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Posted by sukarno on April 30, 2005, at 10:35:49
In reply to Re: Expired medications... safe to take? » sukarno, posted by pro_social_soon on April 30, 2005, at 7:37:59
Hi there. :-)
I'm back up to the manufacturer's recommended dose of 12.5mg 3x a day.
Other meds I take are Xanax 1mg 3x/day and 1.5 to 2mg at bedtime; famotidine (Pepcid) 20mg every 6 hours for acid reflux.
I've found Stablon to reduce the effectiveness of Xanax and have had headaches and nightmares which haven't gone away with prolonged use (of Stablon).
I'm about to give up on the Stablon "experiment" because of the headaches (a chronic, vascular headache in the temples and front part of the head that starts up after my 2nd pill of the day in the late afternoon and goes away by morning) and nightmares/vivid dreams.
It also hasn't lifted me out of my amotivational syndrome despite its antidepressant effect.
The good side is that I feel better in terms of less anxiety/worry, less asthma symptoms and no depression whatsoever.
I think the headaches are just too much, so I'm going to try Survector (amineptine) next at a low dose (maybe 25 to 50mg to start) and have a liver function test.
I'm also contemplating a Xanax withdrawal via gradual Valium substitution and taper.
Xanax just isn't effective enough on Stablon. Even higher doses don't do much good. I feel I probably need a longer acting benzo if I'm going to be on antidepressants.
I just hope Survector doesn't give me headaches! :-)
Overall, I'd say Stablon is excellent for depression and also somatic complaints or accompanied excessive worrying..and possibly even good for panic attacks!
Has anyone else here had headaches on Stablon? You know how a caffeine withdrawal headache is eh? It's exactly like that, except I don't drink coffee or any caffeinated beverages.
Thanks for writing. I hope others can find Stablon useful. I don't think taking paracetamol or ibuprofen on a daily basis would be a good idea just to reduce the headaches caused by it.
Posted by ed_uk on April 30, 2005, at 14:07:30
In reply to Stablon experiment coming to an end., posted by sukarno on April 30, 2005, at 10:35:49
It's seems you've had a love-hate relationship with Stablon! I hope Survector works well :-) Did you ever find out whether it is still being manufactured in Indonesia?
When will you be starting Survector?
Posted by sukarno on April 30, 2005, at 15:14:10
In reply to Re: Stablon experiment coming to an end. » sukarno, posted by ed_uk on April 30, 2005, at 14:07:30
Hi Ed! :-) Great to see you back here again. How are you doing? Are you still on lofepramine?
Yeah, too bad about the headaches. The headache did seem to dissipate quite a bit when I took another Xanax. Maybe I should try taking more benzos if that will help the headaches and night terrors?
Maybe I should just go straight to Survector though.
I still haven't heard from that doctor friend of mine. She is so busy. I did call the pharmacy that she recommended, but just got voice mail, so I sent her an SMS (text message) to ask the pharmacist for some Survector.
I'll just try my best to speak the local language with the pharmacist and find out if it is being locally produced. That would be great if it was! :-)
Putting things into perspective, abuse and liver damage are quite rare when compared to the possible millions of prescriptions which were filled for Survector over a 20 year period.
I really need something to give me a healthy motivation. Survector seems to be good at doing that from what I've read.
I hate to be my own doctor, but the pdocs here, just as in the US, are all on the SSRI bandwagon. When it comes to panic disorder, they are even less knowledgeable.
I know what I'll do... I'll ask my wife to translate into Indonesian language what I need to ask the pharmacist about whether it is being produced locally. That oughta do the trick! Or just go there in person. :-)
I'm really looking forward to having a normal life for once... it has been 17 years of a somewhat non-existance. :(
Posted by ed_uk on April 30, 2005, at 16:14:25
In reply to Re: Stablon experiment coming to an end., posted by sukarno on April 30, 2005, at 15:14:10
>How are you doing? Are you still on lofepramine?
I'm ok thank you :-) I stopped the lofepramine a couple of weeks ago, I haven't had any withdrawal symptoms. I'm not taking any medication at the moment. I might go back on medication in the future but only if I find someone who is willing to prescribe something other than an SSRI or Effexor! A stimulant might help me but only if it didn't cause anxiety, obsessiveness or 'hyperfocusing'.
>Maybe I should try taking more benzos if that will help the headaches and night terrors?
You might have more side effects if you do :-(
Does paracetamol help the headaches?
>I still haven't heard from that doctor friend of mine.
Keep texting! Do people even say 'texting' in other countries? I've been wondering whether it's a 'UK thing'.
>I'll ask my wife to translate into Indonesian language.......
Is your wife Indonesian?
Posted by sukarno on May 1, 2005, at 3:24:03
In reply to Developing side effects to tianeptine (Stablon), posted by sukarno on March 25, 2005, at 5:30:58
I have confirmed that Survector is manufactured locally here in Indonesia. The supply is not limited. Pharmacist said it is only being produced in Indonesia. I think it is still being made for Servier (the local pharmaceutical company has a license from Servier to produce it here...that's my guess). That's all I can say on Dr. Bob's site.
You'll have to email me if you want to know more. xxx
Posted by ed_uk on May 1, 2005, at 11:43:36
In reply to Survector, posted by sukarno on May 1, 2005, at 3:24:03
>I have confirmed that Survector is manufactured locally here in Indonesia. The supply is not limited.
Wow! Do you think you'll be starting Survector soon?
Posted by sukarno on May 1, 2005, at 13:57:20
In reply to Re: Survector » sukarno, posted by ed_uk on May 1, 2005, at 11:43:36
Hi Ed! :-)
I'm not sure when I'll start taking it, but I just ordered 30 tablets (5 strips of 6 tablets each, 100mg) from the pharmacy and he should deliver tomorrow or the next day. He said he'll call me if there's a problem.
When I asked about diazepam, he didn't want to have anything to do with that and said, "diazepam is illegal drug." but after explaining that I could produce a prescription for it he said it is ok, but he doesn't stock that.
Funny thing is that he will sell me Xanax without a prescription. Weird...
At least I can get Survector from this guy without any hassles. I can get diazepam from another pharmacy I guess. I'm just afraid to go to a GP or pdoc and say, "Hey, well, you know I was thinking about quitting Xanax and Prof. Heather Ashton says 1mg Xanax is equivalent to 20mg diazepam for purposes of tapering...." Well, I think I would have a hard time finding a doc who would give me 80mg of Valium a day. *lol*
If I wasn't on Stablon or Survector then I would be ok with just Xanax, but Stablon has enough of a "stimulant" effect that Xanax can't keep away the night terrors caused by it (unless I take a double-dose at bedtime of 2mg) and it seems much more short-acting while I am on Stablon. Maybe my body will eventually adjust more to Stablon with time *shrugs* :-( I hope so!
It's just the headaches (they weren't so bad today) and the vivid dreams/night terrors which are the problem.
Xanax just won't cover for the nighttime anxiety in the prescribed dose of 1mg 4x/day.
I suppose I could remain on Xanax for daytime use and take something like Rivotril or Valium for nighttime to suppress night terrors? What would you do?
Is that a good idea? I hate to be my own doctor, but I've seen the psychiatrists here and they are equally or more clueless than the ones back in the states.
So far, so good with the depression though! I feel happy! :-)
Posted by ed_uk on May 1, 2005, at 15:48:06
In reply to Re: Survector, posted by sukarno on May 1, 2005, at 13:57:20
>When I asked about diazepam, he didn't want to have anything to do with that and said, "diazepam is illegal drug." but after explaining that I could produce a prescription for it he said it is ok, but he doesn't stock that.
It's strange how opinions are so different in different countries. Here, diazepam is THE benzo for anxiety. Lorazepam is the benzo which docs won't prescribe. To be fair, all benzos are stigmatised here. My old pdoc *never* prescribed any other benzos for anxiety apart from diazepam.
>I suppose I could remain on Xanax for daytime use and take something like Rivotril or Valium for nighttime to suppress night terrors?
You could try taking Xanax three times a day and Rivotril in the evening. Do you still have no motivation?
Posted by sukarno on May 1, 2005, at 19:05:38
In reply to Re: Survector » sukarno, posted by ed_uk on May 1, 2005, at 15:48:06
Hi Ed. :-)
Is it difficult to get diazepam in the UK if you have an anxiety disorder such as panic disorder or something similar?
I wonder what would happen if I visited the UK and told them I am on Xanax. Would they switch me over to diazepam right away? hehheh.
I still don't feel any motivation, even though I did indeed feel a bit "high"/euphoric after taking the 3rd dose of Stablon 5 hours ago.
I was reading some French website about Stablon where a French doctor was giving his opinion of it. He was saying that it isn't well-studied and only a minority of patients benefit from it, and because there are many other "proven" antidepressants already on the market, he doesn't prescribe Stablon.
Another doctor there said it was more of a "light" antidepressant and is well-tolerated.
It certainly doesn't feel like a strong antidepressant...I'd have to agree there. However, it has helped my depression quite a bit.
Posted by ed_uk on May 1, 2005, at 20:28:28
In reply to Re: Survector, posted by sukarno on May 1, 2005, at 19:05:38
>Is it difficult to get diazepam in the UK if you have an anxiety disorder such as panic disorder or something similar?
Yes, it's difficult. On the other hand, some docs will prescribe a few 2mg diazepam tabs to take 'when required'. Few patients take more than 6mg diazepam per day. High doses raise eyebrows, it is very uncommon for anyone to be prescribed more than 30mg/day. Many docs refuse to prescribe even short-term diazepam treatment for severe anxiety. Most UK docs believe that benzos are always ineffective in the long term, only a few docs accept than some patients don't develop tolerance to the anxiolyic effect. Some people are forced to withdraw from diazepam, even if they've been benefitting from it for many years. They will be told, 'it's not helping you' and the treatment will be withdrawn. The chance of finding a doc in the UK who's willing to prescribe 80mg diazepam is virtually zero. Xanax is not available on the NHS, it's 'black listed', most docs will not have heard of it. You would probably be prescribed diazepam 2mg three times a day for a few weeks and then the treatment would be withdrawn.... You would then be prescribed an SSRI.
Posted by sukarno on May 2, 2005, at 3:39:14
In reply to Re: Survector » sukarno, posted by ed_uk on May 1, 2005, at 20:28:28
Oh my God... that's horrible. What started all the benzophobia in the UK? I had heard that the Church of Scientology and the anti-drug Dr. Peter Breggin were behind some lawsuits there not too long ago.
So, they can basically just take me off my medication cold turkey.... that could be deadly in the case of alprazolam (Xanax) because of seizures. The least of the withdrawal would be a trauma that the patient would never forget.
Is it common for people to go to the Netherlands to get their benzos? Is the UK strict about British citizens bringing back medications from the Netherlands and other countries?
Professor Heather Ashton resides in Newcastle and she was giving out that protocol to switch patients from Xanax to Valium and then tapering them off over a 1 year period or so.
Can she prescribe medications or is she just a lecturer?
Posted by sukarno on May 2, 2005, at 4:19:56
In reply to Re: Survector, posted by sukarno on May 2, 2005, at 3:39:14
I just found out from the pharmacist some disturbing news. :-( :-( :-(
He just told me by SMS (text message), "I am very sorry Mr. Paul, after I called by phone the man who distribution this medicine to me, he said the Survector tab has been expired for all."
I told him I will buy it even if it is expired. Maybe his definition of expired means "gone"?
I hope it just means it is past the expiration date!
Well, I SMS'd my doctor friend and asked her to check more pharmacies.
Maybe it was discontinued here, but in the year 2004, it was still being manufactured here.
I'm sure there is a huge stockpile...unless they destroyed it. I hope not!
I really hope this can be resolved soon, because I want to get good treatment for my amotivation syndrome since I cannot tolerate SSRIs or classic TCAs.
If I can't get Survector, is Adderall (amphetamine salts) a good idea?
Ed? What's your take on this? Would amphetamine in low doses be good for amotivational syndromes and depression?
I'm desperate to try anything to help my lack of motivation and depression.
Posted by Chairman_MAO on May 2, 2005, at 10:28:27
In reply to Survector expired, posted by sukarno on May 2, 2005, at 4:19:56
Amphetamine is certainly good for motivation. A good dose to start with as an adult is 30mg/day in divided doses.
I'm sure people are tiring of my Parnate plugging, but honestly from what you describe it sounds like a good drug for you. :) If they have it in indonesia I would look at it. Also, do you have nomifensine, medifoxamine, or minaprine on the market there? Those also have a significant dopaminergic effect.
Posted by ed_uk on May 2, 2005, at 10:48:00
In reply to Survector expired, posted by sukarno on May 2, 2005, at 4:19:56
>What started all the benzophobia in the UK?
They got a lot of negative publicity on TV (a long time ago). They were often very carelessly prescribed in the 60s, 70s and early 80s. There was a massive backlash because so many people found that they were physically dependent on their medication. In some cases, these people never needed a benzo in the first place. People were prescribed benzos to treat everything from mild headaches to period pain.
Btw, Seroxat was the last drug to receive bad publicity in the UK. Effexor hasn't received any bad publicity yet, most people will not have heard of it. Doctors are prescribing a lot of Effexor at the moment, I imagine there'll be a documentary about the withdrawal symptoms soon!
>Is it common for people to go to the Netherlands to get their benzos?
I doubt it but I don't know. Benzos can be purchased without a presciption in certain European countries, I have no idea about the Netherlands but I would imagine that they are prescription-only.
>Can she prescribe medications or is she just a lecturer?
Presumably she can prescribe, she used to run a benzo withdrawal clinic.
No!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! I wouldn't buy any unless you can ensure a supply for the future.
Have you ever tried an MAOI? Phenelzine (Nardil) or tranylcypromine (Parnate). Are they available in Indonesia? If not, you might be able to import.
Posted by rod on May 3, 2005, at 5:36:17
In reply to Re: Survector, posted by sukarno on May 1, 2005, at 19:05:38
> I was reading some French website about Stablon where a French doctor was giving his opinion of it. He was saying that it isn't well-studied and only a minority of patients benefit from it, and because there are many other "proven" antidepressants already on the market, he doesn't prescribe Stablon.
> Another doctor there said it was more of a "light" antidepressant and is well-tolerated.
he there, vienna calling :-)
Yes exactly. I live in Austria and doctors say the same here. They did not have much success with Stablon, and they rarely use it anymore. Also the insurance "caontrolles" the drug, because for most patients its a waste of time and for the insurance a waste of money. But if you tried nearly everything else, they grant permission to get it.
And its the same here like anywhere else. Effexor is quite the most prescribed AD here....
Posted by sukarno on May 3, 2005, at 6:31:22
In reply to Re: Survector expired » sukarno, posted by ed_uk on May 2, 2005, at 10:48:00
Hi Ed! :-)
How are you doing now? Are you still off medication? I went off nortriptyline abruptly years ago and the only "withdrawal" effect I felt was a sensation of pressure in the head, but that didn't happen all the time. I wonder if you are experiencing any withdrawal reactions from discontinuing lofepramine.
"Btw, Seroxat was the last drug to receive bad publicity in the UK. Effexor hasn't received any bad publicity yet, most people will not have heard of it. Doctors are prescribing a lot of Effexor at the moment, I imagine there'll be a documentary about the withdrawal symptoms soon!"
Is it difficult to get Seroxat now in the UK?
Effexor has a nasty reputation among patients with regards to withdrawal symptoms/reactions upon tapering or rapid/abrupt discontinuation. I'm sure they'll restrict that one too in due time.
Do you know if amphetamine is metabolised by CYP2D6?
Oh, last night I had a severe headache...well, I've had headaches for the entire month I've been on Stablon and last night was too intense for me so I went to two different doctors. The first doc said my BP was 140/80 and prescribed captopril 12.5mg but I didn't take it. I took another Xanax instead and an hour later I got a second opinion at another clinic and my BP was 120/80.
He prescribed tramadol 50mg, but I didn't fill the prescription because I'm afraid of side effects.
I wonder if tramadol is metabolised by 2D6... I was reading that it is pain killer, but also a mild inhibitor of reuptake of norepinephrine and serotonin, so taking it with TCAs can increase the risk of seizure. (I read that from Rxlist.com)
I've never tried MAOIs because of the strict diet. I've heard of people having hypertensive crisis even though they didn't eat tyramine-rich foods and reports of liver damage with phenelzine. Hmm... then again, I've heard that phenelzine is great for panic attacks. Seems risky because I am already prone to fluctuations in BP.
I remember before I was on medication for anxiety and panic disorder that I had BP of 145/90.. I was quite nervous though. After getting on Tranxene the BP went down to normal but over the years my BP has risen..not to what anyone would consider "high". I think the highest I've seen it is 150-something/95 when I was having severe headaches from low dose Effexor (6.25mg).
I asked my doctor friend to help me find Survector since I know it was produced here in 2004, so she said she called the pharmacist and he is checking other pharmacies.
I wonder if manufacturer destroys the drug when it is expired and/or banned.. or if they sell the remaining stock. I'm not sure, but I hope I can at least try a small amount to see if I'll have headaches or other side effects.
It is strange that Survector was made the "black sheep" and scapegoated like that, when drugs of abuse like Xanax are still widely prescribed in almost all countries. Despite all the misprescribing of Valium, that was never pulled off the market despite reports of jaundice and abuse, but with Survector the whole world went nuts over a few hundred cases of abuse and liver problems... the vast majority did just fine on it.
I guess the SSRI manufacturers saw Survector as a threat to their market share and pushed the FDA and WHO to have it withdrawn.
It's sad to read stories where antidepressants have failed people, but Survector helped them....yet they struggle to find it because of their government's decision to ban it.
Very unfortunate. Barbiturates are still on the market. hmm... but they target Survector... sorry for the rant, it just seems fishy to me why it was pulled.
p.s. I have found that Survector is still being produced in Uruguay and Brazil...that is confirmed. I might check with the Philippines too, since they still sell methaqualone (Quaalude/Mandrax/Revonal)..I figure if they still sell rubbish like that, they should sell Survector.
Posted by sukarno on May 3, 2005, at 7:27:03
In reply to Re: Survector expired, posted by sukarno on May 3, 2005, at 6:31:22
"..... Rasagiline (Agilect, Azilect) is a potent, selective, irreversible monoamine oxidase (MAO) type-B inhibitor. It is a useful agent in the symptomatic treatment of Parkinson's disease. Rasagiline and its analogues are under investigation for Alzheimer's disease. They apparently enhance memory and learning. Rasagiline may also improve mood, motivation and age-related memory decline in the ageing but nominally well adult population.
Rasagiline was first synthesised and developed by the Iranian-born Israeli researcher, Professor Moussa Youdim. It will shortly be licensed for sale by Teva Pharmaceuticals under the brand name Agilect in the USA and Azilect in Europe. In the USA, Agilect will be co-promoted with Eisai, Inc, but Eisai upper management are reportedly resisting an FDA request for a [probably unnecessary] "black box" warning on the labelling. In Europe, Azilect will be co-promoted by Danish-based drug giant Lundbeck. Barring unexpected hitches, rasagiline is expected to gain a product license in the first quarter of 2005. Professor Youdim believes that a few years hence we may mix a spoonful of drugs into our daily cereal bowls to protect the brain from neurodegenerative disease. Possibly in future we will take a cocktail of neuroprotective pills to retard the ageing process itself. Pitfalls doubtless lie ahead, and timescales may prove optimistic; but neither senescence nor age-related disease are inevitable.
Rasagiline can be taken orally both on its own in early Parkinson's disease, and as an adjunct to levodopa (L-DOPA) treatment in later stages of the disorder. There is tentative evidence that rasagiline can slow the progression of Parkinson's disease itself as well as offer symptomatic relief. This has been shown in vitro and in non-human animals, though not yet conclusively in controlled clinical trials of human subjects.
Parkinson's disease is a degenerative disorder of the central nervous system of unknown origin. Both environmental and genetic factors play a role in its onset. Symptoms include stiffness, tremors, slowness of movement, impaired balance, decreased facial expression, fatigue, apathy and sometimes pain. A slowing down of mental processes is sometimes mistaken for dementia; but as a rule of thumb, "if you give a Parkinson's patient time to answer a question, they will answer. If you give an Alzheimer's patient time to answer a question, they will forget the question".
Parkinson's disease is often foreshadowed by diminished vitality and depression. These tend to worsen as the disease progresses. Some 50% of Parkinsonians become clinically depressed; there is accumulating evidence that the depressive symptoms of "dopamine deficiency disorder" are directly tied to the neuroanatomical degeneration.
Overt signs of Parkinson's disease are associated with an 80%-plus loss of dopamine-producing neurons in the substantia nigra of the midbrain. Sub-clinical signs and symptoms may appear earlier. Some researchers suspect that all of us would all go on to develop Parkinsonian symptoms if we lived long enough. This is because of disproportionate nigral dopamine cell loss during every decade of adult life. Increased dopamine catabolism is associated with oxidative stress and neuronal cell death. Selective MAO-B inhibitors delay this process, but the molecular mechanisms of neuroprotection appear to be independent of MAO-B inhibition itself, lying in the interference by propargylamines with apoptosis signalling pathways.
By inhibiting MAO-B, rasagiline prevents the deamination of the monoamines dopamine and phenethylamine (PEA), thereby increasing their concentration in the synapse and curbing production of the reactive oxygen species, hydrogen peroxide. High concentrations of hydrogen peroxide are associated with increased oxidative stress. Rasagiline both raises levels of striatal dopamine produced from levodopa and improves the survival prospects of ailing dopaminergic neurons themselves. This salvage job helps restore a measure of normal locomotion, gait and coordination in Parkinsonian patients while delaying their physical decline.
In the brain, dopaminergic neurons in the substantia nigra project to the basal ganglia. The basal ganglia regulate bodily movement, but also play a role in thinking and emotion. To function adequately, basal ganglia cells require a proper balance between the dopamine and acetylcholine signalling systems. This balance is lost in Parkinson's disease as the dopamine neurons die off. Parkinson's patients are sometimes given anticholinergic drugs like benztropine (Cogentin), trihexyphenidyl (Artane), and ethopropazine (Parsitan) to control their tremor. At worst, these drugs are dementing; at best, they impair memory and cognition. Anticholinergics were the mainstay of treatment before the advent of levodopa. Fortunately, the benefits of rasagiline, either as monotherapy or an adjunct to levodopa treatment, extend beyond restoring motor activity. For rasagiline (modestly) improves cognitive performance on a range of tests, suggesting a role in improved central cholinergic function that is still obscure. More speculatively, a low-dosage regimen of rasagiline may prevent or retard the onset of Parkinsonian symptoms, dementia and diminished vitality in the wider, notionally healthy community as a whole. Such usage is likely to remain off-label for the foreseeable future.
The main therapeutic advantage of rasagiline over the other selective irreversible monoamine oxidase-B inhibitor selegiline (l-deprenyl, Eldepryl) is that rasagiline does not have the perhaps toxic amphetamine metabolic breakdown products of the structurally similar selegiline. Selegiline is metabolised to R(-)-methamphetamine and R(-)-amphetamine, whereas rasagiline is metabolised to R(+)-1-aminoindan. There is no evidence that these trace amphetamine metabolites contribute to selegiline's neuroprotective action.
Both selegiline and rasagiline are neuroprotective via multiple mechanisms that are poorly understood. However, their role in stabilising mitochondrial membrane potential is critical. The propargylamine moiety rather than MAO inhibition per se apparently holds the key to their neuroprotective action: the S isomer of rasagiline is some 1000 times less potent as an MAO inhibitor, but it's still protective against neurotoxic insults. Rasagiline inhibits activation of the apoptotic cascade triggered by dopamine neurotoxins and oxidative stress. Apoptosis is an active process of programmed cell-death induced by exposure to neurotoxins. Rasagiline and other propargylamines can rescue deteriorating dopaminergic neurons by inhibiting the "death signal" transduction-mechanism of mitochondrial permeability transition. Current evidence suggests that rasagiline may be more effective than selegiline in salvaging dopamine nerve cells from the usual neurological carnage of later life.
Chronic rasagiline use increases the activity of the antioxidative enzymes superoxide dismutase (SOD) and catalase (CAT), both in the dopaminergic systems of the brain and also in the heart and kidneys. Professor Youdim speculates that one day rasagiline will be used not just as a prophylactic against neurodegenerative disease but as a cardioprotectant.
Rasagiline is typically well tolerated if used within the therapeutic dosage range. In one study, the efficacy of 1mg rasagiline taken once daily was similar to 200mg of the COMT inhibitor entacapone (Comtan) administered with each levodopa dose: the only adverse event reported to be significantly more common with rasagiline than with the placebo was postural hypotension. Professor Youdim, profiled in Haaretz, observes that rasagiline [taken at a low MAO-B selective dosage] typically has no adverse side-effects. Most recently, the well-controlled PRESTO study of the Parkinson Study Group confirmed an improvement in motor fluctuations and Parkinson's disease symptoms in levodopa-treated patients; the only adverse events significantly more common with rasagiline than with the placebo were reportedly balance difficulties in the 0.5 mg rasagiline group, and anorexia, vomiting and weight loss in the 1 mg group. Fewer patients reported depressive symptoms. In the LARGO study, the frequency of adverse side-effects in patients using rasagiline or entacapone as adjuncts to levodopa treatment was similar to those in patients taking the placebo. At dosages above around 2mg per day, rasagiline loses its selectivity for MAO type B and also inhibits MAO type A. An MAO-B selective regimen does not cause significant tyramine potentiation, the dreaded "cheese effect" common to users of older unselective and irreversible MAOIs who eat tyramine-rich foods. Thus low-dosage rasagiline demands no special dietary restrictions.
The optimal dosage of rasagiline has yet to be exactly established, whether for Parkinsonians, or for depressives who may benefit from higher rasagiline dosages that inhibit both types of MAO enzyme, or for use of rasagiline prophylactically as a neuroprotectant by the "worried well", i.e. sufferers from the fatal hereditary disorder we know as the ageing process. Over the clinical dosage range, rasagiline displays a more-or-less linear pharmacokinetics. An excessively high dosage of rasagiline apparently shrinks the cell sizes of nigral tyrosine hydroxylase-positive neurons. This is currently of unknown significance, but suggests a dose-effect graph with an inverted U shape, possible toxicity, and consequently the need for caution.
The effects of a long-term regimen of rasagiline on human life-expectancy and maximum lifespan are unknown. Yet since selegiline can increase both life-expectancy and maximum lifespan in a number of non-human animal species, it is possible, though again unproven, that rasagiline's superior metabolic profile may offer advantages for life-extension. The only other current routes to enhanced longevity are either caloric restriction (CR) - which takes brutal self-discipline and can compromise mood, virility and vitality - or, hypothetically, the use of compounds like resveratrol which mimic the effects of caloric restriction without provoking its troublesome side-effects. But they remain clinically unproven too.
Rasagiline doesn't displace catecholamines from their intracellular stores. It lacks any significant "abuse potential", though this is seldom a problem with selegiline either. Neither acute nor chronic rasagiline taken at MAO-B selective dosages increase tissue levels of the monoamine neurotransmitters noradrenaline, serotonin and dopamine. In common with selegiline, rasagiline may be protective against the serotonergic damage caused by the widely used drug MDMA (Ecstasy). Unfortunately, the risks of taking any MAOI with MDMA probably statistically outweigh any neuroprotective benefit. A post-E fluoxetine (Prozac) or other SSRI may offer a less hazardous form of neuroprotection; but this carries theoretical risks too. Until safe and sustainable insight-and-empathy drugs are developed, it may be prudent either to use them only very sparingly or avoid them altogether. An enriched conception of mental health is of limited use until we have the means to sustain it.
If rasagiline is good news, then other pharmaceutical products on the horizon are better. Perhaps most notable is the neuroprotectant ladostigil (TV3326), again designed by the redoubtable Professor Youdim. Ladostigil inhibits both cholinesterase and MAO activity, enhancing cognition and mood alike. Ladostigil is cunningly designed with a propargyl group for MAO inhibition and a carbamate moiety to inhibit cholinesterase. Both the MAO type A and MAO type B inhibition of ladostigil are relatively selective to the brain: liver and small intestine enzymes are less affected.
This advance is important for several reasons. One reason is obviously the plight of a rapidly growing population of elderly Parkinsonian and Alzheimer's patients in need of more effective drug therapies with fewer risks and adverse side-effects. But the potential range of therapeutic application is broader. Most people would like to feel happier, smarter, younger and sexier. Sadly, contemporary antidepressants and nootropics are badly flawed. It's not just that they are often ineffective. They either have anticholinergic "dumb drug" effects like the older tricyclics, or they flatten emotions and kill libido, like the SSRIs. Older unselective, irreversible MAOIs like tranylcypromine (Parnate) and phenelzine (Nardil) can elevate mood, but their risks and accompanying dietary restrictions make them unattractive even for the clinically depressed and their wary physicians. Meanwhile classic nootropic agents such as cholinergic boosters are liable to subdue mood and cause behavioural inhibition. The attraction of dual action agents like ladostigil, on the other hand, is that they promise to lift mood and intellectual performance alike, while offering a measure of protection against the ravages of ageing.
Even so, tomorrow's neuroprotective smart mood-brighteners are just stopgaps. They offer only palliative relief on the route to germ-line gene therapy in decades to come, and perhaps the wholesale genomic rewrites of the era beyond. The global pandemic of human ageing can ultimately be cured; but eradicating the lethal disorder we call old age may still take several centuries. In the meantime, rasagiline and its derivatives are potentially valuable drugs that can improve the quality of life of sick and ageing Darwinians in the years ahead ...."
Posted by sukarno on May 3, 2005, at 17:33:36
In reply to Re: Stablon (tianeptine) and hepatotoxicity » sukarno, posted by ed_uk on April 24, 2005, at 12:00:30
Tianeptine treatment induces regionally specific changes in monoamines.
Frankfurt, McKittrick, McEwen, Luine
Encephale 1995 Oct, 23 696 (1-2)1-6
Tianeptine is an atypical tricyclic antidepressant that facilitates serotonin (5-HT) reuptake. Tianeptine (10 mg/kg) or saline was administered intraperitoneally to male rats daily for 4 days. Monoamine levels were measured in micropunches of discrete brain nuclei that are implicated in mood and cognition. In addition, the rates of 5-HT and norepinephrine (NE) accumulation were determined by the pargyline method. Few changes were noted in the 5-HT system. 5-HT levels were increased by short-term tianeptine in the CA3 region of hippocampus, and 5-hydroxyindoleacetic acid (5-HIAA) was increased in the ventromedial nucleus of hypothalamus, while 5-HT turnover was decreased in preoptic area (POA). In addition, short-term tianeptine treatment increased NE levels in POA, parietal sensory cortex (SCTX) and dorsal raphe (DR), and decreased NE in dentate gyrus. NE turnover was also decreased in DR, SCTX and parietal motor cortex. These data suggest that the short-term neural and behavioral actions of tianeptine may be attributable, in part, to alterations of the norepinephrine system.
Maybe this is why I have an "Effexor headache" and slightly raised BP. I had no idea that Stablon (tianeptine) increased norepinephrine levels and that this is the mechanism of action with regards to its antidepressant effect.
Servier says it works on the HPA axis (Hypothalamic-Pituitary-Adrenal axis), reducing its response to stress, among other things, but no mention on their website about norepinephrine.
One would think that by increasing NE, you would help motivation, but that didn't happen to me.. I still feel a serious lack of motivation.. but at least I'm not depressed.
I lowered the dose to 2 tablets a day after I had that severe headache 24 hours ago.
When I woke up I felt "slowed down" and when I moved my head it felt like a strange sense of vertigo..(room felt like it was moving when I moved my eyes or head.. a slight "visual lag" I suppose... but that's stretching it). I certainly felt depressed until an hour or so after I took the first Stablon of the day.
I wonder if this headache is dangerous.
Posted by hok on May 3, 2005, at 18:23:25
In reply to Rasagiline (Azilect) useful for motivation?, posted by sukarno on May 3, 2005, at 7:27:03
anybody tried it yet? it's supposed to be like selegiline but without the amphetamine metabolites. I guess it won't be available in europe or the u.s. until later this year. I was only able to find it online through some of the pharmacies in Israel, where it was recently launched.
Posted by sukarno on May 3, 2005, at 19:07:56
In reply to Re: Rasagiline (Azilect) useful for motivation? » sukarno, posted by hok on May 3, 2005, at 18:23:25
So you can buy it from an Israeli online pharmacy? I might try that.
My interest in dopamine agonists stems from persistent lack of motivation and low libido. I don't suffer from erectile dysfunction (impotence) though, just lack of interest.
Does anyone here find dopamine agonists or dopamine reuptake inhibitors (e.g. Survector...how I wish I had that! argh!) useful for increasing libido (sex drive)?
I think Stablon may have helped, but only marginally.
A lot of people say l-deprenyl (Eldepryl/selegiline) and Dostinex (cabergoline) are great for reviving one's sex life, in addition to helping boost motivation and lift depression.
Posted by sukarno on May 3, 2005, at 23:04:40
In reply to Survector, posted by sukarno on May 1, 2005, at 3:24:03
I just called PT Darya-Varia Laboratoria, the local manufacturer of Survector and they informed me that it is no longer being produced here, so they told me to call Servier, which I just did.
Servier told me that they quit making it "a long time ago" but they have a new one called "Stablon"... that wasn't news to me.
Anyway, I went to Servier's website and they have a Parkinson's drug which boosts dopamine D2 and D3 and also norepinephrine! :-)
Sounds like a good Survector substitute I suppose, because Survector boosted dopamine and also norepinephrine and serotonin (somewhat).
This is a link to product information of Trivastal (Piribedil):
Might be worth a shot.
Posted by ed_uk on May 5, 2005, at 6:16:15
In reply to Re: Survector expired, posted by sukarno on May 3, 2005, at 6:31:22
>How are you doing now? Are you still off medication?
I'm ok thank you, no withdrawal symptoms :-) I won't be going back on lofepramine in the near future.
>Is it difficult to get Seroxat now in the UK?
It's still prescribed a lot, some docs prescribe it like candy... others are more cautious.
If you stick to the appropriate diet, Nardil reduces blood pressure.
>I have found that Survector is still being produced in Uruguay and Brazil...
Is that definite? I thought they were just using the remaining stocks in Brazil.
Posted by sukarno on May 5, 2005, at 8:51:58
In reply to Re: Survector expired » sukarno, posted by ed_uk on May 5, 2005, at 6:16:15
Hi Ed! :-)
I've always wondered why Nardil and TCAs such as imipramine are more effective at blocking panic attacks, because SSRIs and many other drugs target the same neurotransmitters as the older MAOIs and TCAs.
Is there some mode of action that Nardil and Tofranil (imipramine) have that is separate from their effects on 5-HT and to a lesser extent NE that causes them to have much higher efficacy than the SSRIs?
I remember that imipramine was heavily sedating and that was good for me because I needed a good night's sleep after all that anxiety and panic. I've heard Nardil is not sedating though.
Tofranil is said to be the gold standard in treating panic disorder anyway (or used to be).
Survector is still being produced in Uruguay according to an online pharmacy, but I'd bet that they are wrong about it after doing more searching on Google.
I think it was forced off the market due to the SSRIs. I've never heard of a medication that was on the market for 21 years and then suddenly pulled like that.
We, the sufferers/victims of anxiety/depression, are not the ones who are considered when the big decisions are made by the top drug companies, etc.
I remember when I had told the first psychiatrist I saw here in Indonesia about my panic disorder, he ignored what I had said about my bad reactions to SSRIs and prescribed me Zoloft anyway. Of course I didn't fill it.
I'm still taking Stablon, but lowered the dose to 2 tablets a day.. headache is much improved. Is that headache caused by serotonin?
I feel quite depressed though. I'm hoping to find some antidepressant that will work and not be chock full of sexual side effects or anxiety like SSRIs or the cardiotoxicity of TCAs, etc.
I guess I'm afraid to try Nardil. What foods _can_ I eat on Nardil? I know to avoid tyramine-rich foods, but what I eat now is:
baked beans, spaghetti noodles, high fiber wheat bread, olive oil.
That's my vegan diet. lol... Is that free of tyramine?
Thanks Ed. I think you are a psychopharmacologist in reality, eh? hehheh. You know your stuff about medications and mechanisms of action, etc.
Posted by Chairman_MAO on May 5, 2005, at 16:54:45
In reply to Re: Survector expired, posted by sukarno on May 5, 2005, at 8:51:58
After approximately a three-day adjustment period where I had some mild "brain shocks" and emotional lability, the 75mg phenelzine I switched to from the 120mg tranylcypromine kicked in. Wow, I am impressed! It's a lot like the mild euphoria the parnate gave me without any of the stimulant side effects. I still do miss Parnate's DA "push" that gave me a little extra motivation and "go get em'" attitude, but I am really loving how calm I am. Also, my libido is slightly dampened, but performance and the enjoyment of "the act" are intact. Pretty nice. Now, if I don't start gaining weight exponentially, I'll be all set! My sleep is also vastly improved on phenelzine over tranylcypromine.
I really can't say enough good things about the irreversible MAOI + buprenorphine combination. I really feel someone should do a study of it in treatment-resistant depression or anxiety disorders.
That said, please don't be afraid of the diet nor the drug interactions. It's really very easy to follow. Everyone's different, but I ignore the diet except for the following, which I strictly observe:
1) Fermented Soy Products
2) REAL aged cheeses. Processed cheddar, etc. that one finds in 75%+ of all food in the USA are safe. As a matter of fact, the tyramine reaction was first discovered when MAOIs were introduced in Europe, because their aged foods are actually significantly aged, so people started having terrible headaches and stroking out all over the place. No one really noticed this in the US because most of our food is slop. ;)
3) Tap beer anywhere other than bars that I am certain clean their taps. If I'm going to a savory restaurant, especially one I frequent, I simply explain to the bartender that I am highly allergic to fermented beer residue in the taps and to simply be straight up with me about whether they clean the taps or not. It's never led me wrong yet, probably because no bartender wants to risk a lawsuit after I tell them what the reaction would be. Of course, I always carry around some chlorpromazine just in case (want to get phentolamine amps /w syringe to carry while I travel, but I dont know if doc will rx that, heh)
4) REAL air-dried sausages and aged meats
5) fava/broad beans
That's pretty much it for me. Simply avoid stuff that's really aged, spoiled, or otherwise old, and you'll do fine. You can carry medication with you to abort a hypertensive crisis, too. I think you'll find that, if you respond to an MAOI, you will never want to go back. I have ingested one or more representatives from just about every class of illicit and licit psychoactive drug, and have yet to find something that reliably produces anywhere near as course or robust a mood lift as the irreversible MAOIs. Any drug that's ever come along (at least in the US) that's ever stood a chance at rivaling the MAOIs has been taken off the market because of "abuse potential". I feel today the MAOIs would've never been FDA approved because of abuse potential, but they got in the door before the insanity convention of 1972 when they signed the CSA into law. I'm happy about that, too, because otherwise I would be a more-or-less miserable dysfunctional wreck.
Posted by ed_uk on May 6, 2005, at 5:28:39
In reply to Re: Survector expired, posted by sukarno on May 5, 2005, at 8:51:58
>Is there some mode of action that Nardil and Tofranil (imipramine) have that is separate from their effects on 5-HT and to a lesser extent NE that causes them to have much higher efficacy than the SSRIs?
Nardil raises levels of 5-HT, NE, dopamine and GABA in the brain. Parnate raises 5-HT, NE and dopamine but not GABA. Also, it is important to bear in mind that MAOIs affect 5-HT via a completely different mechanism to the SSRIs.
In addition to 5-HT reuptake inhibition, the noradrenergic properties of imipramine may help to suppress panic attacks.... SSRIs do not share this effect.
>Survector is still being produced in Uruguay according to an online pharmacy, but I'd bet that they are wrong about it after doing more searching on Google.
Can you find out who the manufacturer is, call them, and find out whether they're still making it??
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