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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by Cecilia on September 6, 2009, at 22:48:39
Trying to figure out if there's any point in trying to order agomelatine from overseas. I see it's a 5-HT2b antagonist and a 5-HT2c antagonist, plus melatonin. Seems like the first 2 characteristics are similar to serzone and trazodone, both of which I've tried of course, without benefit; I've tried everything. Anyone knows how agomelatine differs from those? With the liver problems reported with agomelatine, I wonder if it's most like serzone. Plus the added melatonin, can't help but wonder if the AD effect the studies claim is mostly do the improved sleep from that. Melatonin doesn't do much for my severe insomnia, maybe has a slight additive effect to Ambien. And I can't help but worry about a med that involves taking melatonin daily: anyone know if this might cause a decrease in production of your own melatonin? (Seems so strange to me that melatonin is available OTC; it's a hormone, you can't buy other hormones like thyroid or estrogen OTC). Anyone know exactly how agomelatine differs from other AD's besides the addition of melatonin? Cecilia
Posted by Phillipa on September 7, 2009, at 0:43:38
In reply to Agomelatine questions, posted by Cecilia on September 6, 2009, at 22:48:39
I didn't realize melatonin was a hormone hence the autoimmune concerns of some on the site. Phillipa
Posted by ace on September 7, 2009, at 1:48:13
In reply to Re: Agomelatine questions » Cecilia, posted by Phillipa on September 7, 2009, at 0:43:38
> I didn't realize melatonin was a hormone hence the autoimmune concerns of some on the site. Phillipa
Phillipa- did you get my reply?
hope all is well!
Ace, Nardil man, haha
Posted by Netch on September 7, 2009, at 4:31:24
In reply to Re: Agomelatine questions » Phillipa, posted by ace on September 7, 2009, at 1:48:13
Agomelatine causes increased neurogenesis through simultaneous action on 5-HT2C and MT1/MT2 receptors
Posted by Nadezda on September 7, 2009, at 14:58:12
In reply to Agomelatine questions, posted by Cecilia on September 6, 2009, at 22:48:39
Wikipedia says:
"Agomelatine (trade names Valdoxan, Melitor, Thymanax) is an antidepressant developed by the pharmaceutical company Servier. It is known as a norepinephrine dopamine disinhibitor (NDDI) because of its 5HT2C antagonistic properties of inhibiting 5HT, thereby disinhibiting DA and NE release by enhancing the activity of frontocortical dopaminergic and adrenergic pathways.[1][2] Agomelatine is also a potent agonist at melatonin receptors which makes it the first melatonergic antidepressant.[2][3] Because of its unique profile, agomelatine has not been associated with weight gain, sexual side effects, or withdrawal syndrome; this is in contrast to most SSRIs and many antidepressants.[4][5]...
....[6] Agomelatine showed benefits over sertraline and paroxetine due to the lack of sexual side effects and discontinuation side effects. Because of its action upon the melatonin receptors, agomelatine also showed a marked improvement in sleep quality. There were no associated instances of daytime drowsiness.[5] Agomelatine has also demonstrated anxiolytic properties and thus may prove efficacious in the treatment of anxiety disorders.[7]"
another website announcing the European authorization of agomelatine sale says:
"Valdoxan is the result of an extensive pharmacological research programme involving investigation centres all around the world (including the UK), and represents a different approach to the treatment of depression that goes a step beyond the monoamine hypothesis. Valdoxan is an MT1 & MT2 melatonergic receptor agonist with 5-HT2C receptor antagonist properties.9,10 As a result of this novel mode of action, Valdoxan has demonstrated antidepressant efficacy through circadian rhythm resynchronisation and the increase of dopamine and noradrenaline levels.11 This mechanism of action is unlike those of commonly prescribed antidepressants such as selective serotonin reuptake inhibitors (SSRIs), and serotonin and noradrenaline reuptake inhibitors (SNRIs), since Valdoxan has no impact on serotonin levels.1
At the moment I don't have enough to time analyze what this means, but I had heard that it's uses a novel mechanism. Although (not that I want to be skeptical), one always hears that.
Nadezda
Posted by Phillipa on September 7, 2009, at 19:55:39
In reply to Re: Agomelatine questions » Phillipa, posted by ace on September 7, 2009, at 1:48:13
Ace e-mailed you didn't get a reply? Did you take the properties off the one I sent to your address? Love Phillipa
Posted by Cecilia on September 12, 2009, at 2:16:25
In reply to Re: Agomelatine questions, posted by Nadezda on September 7, 2009, at 14:58:12
Interesting, agomelatine acts on norepinephrine and dopamine rather than serotonin? I've never found a norepinephrine stimulating AD that I've been able to tolerate. I wonder if it's the combination with the melatonin that makes it supposedly helpful for anxiety instead of increasing it like most AD's with norepinephrine do. Wouldn't think that would help with anxiety during the day though, just make you sleep better. Cecilia
Posted by Nadezda on September 13, 2009, at 0:19:07
In reply to Re: Agomelatine questions » Nadezda, posted by Cecilia on September 12, 2009, at 2:16:25
I don't know much about it, other than I'm hoping to try it when it becomes available in the US-- if it ever does. If you do try it, I'd like to know how it works, and what effects or side effects it seems to have.
Good luck.
Nadezda
Posted by Sigismund on September 20, 2009, at 1:17:00
In reply to Agomelatine questions, posted by Cecilia on September 6, 2009, at 22:48:39
>Seems like the first 2 characteristics are similar to serzone and trazodone, both of which I've tried of course, without benefit; I've tried everything.
Never tried them, but I doubt that it's like Trazodone. Ago doesn't make me feel yucky.
> Anyone knows how agomelatine differs from those? With the liver problems reported with agomelatine, I wonder if it's most like serzone. Plus the added melatonin, can't help but wonder if the AD effect the studies claim is mostly do the improved sleep from that.Agomelatine has a small comfort factor. That's kind of it....better sleep and a bit of comfort next day as well, without side effects. If it was better (shall we say), people would increase the dose and it would become a drug of abuse.
>Melatonin doesn't do much for my severe insomnia, maybe has a slight additive effect to Ambien.Same here.
Posted by Netch on September 25, 2009, at 3:27:53
In reply to Re: Agomelatine questions, posted by Nadezda on September 13, 2009, at 0:19:07
"Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus.
Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT(2C)) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3beta) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT(2C)) antagonist properties, we determined whether melatonin and 5-HT(2C) receptor antagonists similarly influence cell proliferation and survival. Only the 5-HT(2C) receptor antagonists, SB243,213 or S32006, but not melatonin, mimicked the effects of agomelatine on cell proliferation in VH. The promoting effect of agomelatine on survival was not reproduced by the 5-HT(2C) receptor antagonists or melatonin alone. However, it was blocked by a melatonin antagonist, S22153. These results show that agomelatine treatment facilitates all stages of neurogenesis and suggest that a joint effect of melatonin agonism and 5HT(2C) antagonism may be involved in promotion by agomelatine of survival in the hippocampus. "
This is the end of the thread.
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