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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by medievil on December 10, 2006, at 9:33:10
Poop out is a big issue with many antidepressants and other medications
from my research i came to the conclusion CCK might play a big role in this
apperantly a CCK antagonist reverses tolerance to opiates
also on reading this site there are e few posts regarding naltrexine to reverse SSRI poop out
this might be possible as suppressing opiates it might have a downregulation on CCK, thus reversing poop outif anyone has any information on how poop out happends plzz posts
Posted by medievil on December 10, 2006, at 9:38:59
In reply to neurotransmitter tolerance/poop out downregulation, posted by medievil on December 10, 2006, at 9:33:10
This is something i found, another proof CCK downregulates receptors
Cholecystokinin downregulates receptors for vasoactive intestinal peptide and secretin in rat pancreatic acini
S. Katsushima, H. Adachi, T. Honda, S. Sato, T. Kusui, S. Onishi, E. Aoki, M. Noguchi and J. Konishi
Department of Radiology and Nuclear Medicine, Kyoto University School of Medicine, Japan.We examined the effect of cholecystokinin (CCK) on the receptors for vasoactive intestinal peptide (VIP) and secretin in rat pancreatic acini. CCK decreased the specific binding of 125I-VIP and 125I-secretin by 42 and 51%, respectively. This CCK-induced inhibition was caused by an apparent decrease in the capacity of high-affinity binding sites of VIP and secretin receptors. CR 1409, a specific antagonist of CCK, abolished CCK-induced binding inhibition, whereas 12-O-tetradecanoylphorbol-13-acetate, A23187, and cycloheximide did not affect the binding of the radioligands. Both N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (Bt2cGMP) and nitroprusside inhibited the specific binding of 125I-VIP. This inhibition, however, was because of an apparent decrease in the capacity of low-affinity binding sites on VIP receptors. CCK-induced downregulation of VIP and secretin receptors was associated with the diminished acinar response to VIP or secretin-induced adenosine 3',5'-cyclic monophosphate accumulation and amylase secretion, whereas neither Bt2cGMP nor nitroprusside affected VIP-induced amylase secretion. Data suggest that CCK-induced downregulation is mediated by the initial interaction of CCK with CCK receptors followed by some postreceptor process, which appears unrelated to protein kinase C, calcium mobilization, decrease in protein synthesis, or cellular cGMP increases. This downregulation, at least in part, accounts for CCK-induced restricted stimulation of amylase secretion by VIP and secretin.
Posted by medievil on December 10, 2006, at 9:55:24
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by medievil on December 10, 2006, at 9:38:59
i think i am into something
i have been researching Naltrexone too, and it doesnt seem to be working for everyone, probebly because it doesnt work on CCK directly
i beleive there would be more succes using CCK antagonists directly in preventing AD poop outCCK2 receptor-deficient mice have increased sensitivity of dopamine D2 receptors.
Department of Physiology, Biomedicum, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. sulev.koks@ut.ee
The present study supports a role of CCK(2) receptors in the regulation of dopamine neurones. In pharmacological studies conducted on male CCK(2) receptor-deficient mice the changes in the activity of dopamine system were established. A low dose of dopamine agonist apomorphine (0.1 mg/kg), stimulating the pre-synaptic dopamine receptors, induced significantly stronger suppression of locomotor activity in mutant mice (-/-) compared to their wild-type littermates (+/+). The administration of amphetamine (3-6 mg/kg), a drug increasing dopamine release, caused a dose-dependent stimulation of locomotor activity in wild-type mice. In mice lacking CCK(2) receptors, a lower dose of amphetamine (3 mg/kg) tended to suppress the motor activity, whereas the higher dose (6 mg/kg) induced the significantly stronger motor stimulation in mutant mice. Moreover, in the CCK(2) receptor-deficient mice the affinity of dopamine D(2) receptors, but not 5-HT(2) receptors, was increased. Altogether, the targeted genetic suppression of CCK(2) receptors increased the sensitivity of pre- and post-synaptic dopamine D(2) receptors.
Posted by Tom Twilight on December 10, 2006, at 10:11:03
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by medievil on December 10, 2006, at 9:55:24
This is a fascinating topic Medievel
Its funny that you shoud mention CCK Antagonists.
I'm going to start taking Proglumide, the only comercially available CCK antagonist, to see if it helps with anxiety & more importantly Opiate tollerance.Unfortunatly Proglumide is only a very weak CCK Antagonist so I don't know if it has much affect :(
I'd love to try a Powerful CCK 2 antagonistNote: Proglumide is the only commercially available CCK Antagonist as far as I know, there may be others
Posted by medievil on December 10, 2006, at 10:14:54
In reply to CCK-Anxiety-Opiate tollerance, posted by Tom Twilight on December 10, 2006, at 10:11:03
cck antagonists seem to be VERY effective in reversing tolerance to opiates
i hope Proglumide would have any good effect, i'd say keep me posted :)
Posted by Tom Twilight on December 10, 2006, at 10:19:14
In reply to Re: CCK-Anxiety-Opiate tollerance, posted by medievil on December 10, 2006, at 10:14:54
> cck antagonists seem to be VERY effective in reversing tolerance to opiates
>
> i hope Proglumide would have any good effect, i'd say keep me posted :)Thanks
Thats assuming it arrives at all!
I had to order it onlineSorry can't say where sight rules and all that-Don't want to get banned!
Posted by blueberry on December 10, 2006, at 14:44:15
In reply to neurotransmitter tolerance/poop out downregulation, posted by medievil on December 10, 2006, at 9:33:10
I was thinking that while all the researchers and scientists work on new drugs for depression and anxiety, they are barking up the wrong tree. If they want a true blockbuster seller that would advance the entire medical field in one massive humongous leap, they should conquer the poopout thing.
Posted by linkadge on December 10, 2006, at 15:06:56
In reply to Re: neurotransmitter tolerance/poop out downregulation, posted by blueberry on December 10, 2006, at 14:44:15
Poopout will always occur. Tollerance goes down to the cellular and mitochondrial level. The brain only has so much cellular energy. You can throw all the neurotransmitters around, but in the end the nerve cell can only fire so often. Demanding more of it that it has may just kill it off.
Linkadge
Posted by medievil on December 11, 2006, at 0:13:24
In reply to Re: neurotransmitter tolerance/poop out downregulation, posted by linkadge on December 10, 2006, at 15:06:56
> Poopout will always occur. Tollerance goes down to the cellular and mitochondrial level. The brain only has so much cellular energy. You can throw all the neurotransmitters around, but in the end the nerve cell can only fire so often. Demanding more of it that it has may just kill it off.
>
> Linkadge
>
i beleive poop out can be prevented to balance all neurotransmitters
example: instead increasing dopamine, opiates and serotonin in the brain decrease glutamate, cck and aspartate (dunno about that one) and you might prevent poop out
Posted by medievil on December 11, 2006, at 11:02:08
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by medievil on December 11, 2006, at 0:13:24
allright, CCK doesnt seem to be responsible for the tolerance to serotonin, NK receptors do!
now i'm up to find what causes tolerance to GABASustained blockade of neurokinin-1 receptors
enhances serotonin neurotransmissionBACKGROUND: Antagonists of neurokinin-1 (NK(1)) receptors, through which substance P acts, have been proposed to belong to a new class of antidepressants with a unique mode of action. It was postulated that they exert this putative therapeutic effect independently of the serotonin (5-HT) neurons. METHODS: The aim of the present study was to assess, using in vivo electrophysiological paradigms, the effects of sustained administration of the nonpeptidic NK(1) antagonist CP-96,345 on the firing activity of rat dorsal raphe 5-HT neurons, the responsiveness of pre- and postsynaptic 5-HT(1A) receptors, and overall 5-HT neurotransmission in the hippocampus. RESULTS: Both short- and long-term treatments with CP-96,345 significantly increased the spontaneous firing activity of dorsal raphe 5-HT neurons, and this increase was associated with an attenuation of somatodendritic 5-HT(1A) autoreceptor responsiveness. In contrast, the inactive enantiomer of CP-96,345 at NK(1) receptors, CP-96,344, did not alter these parameters after short-term administration. Because 5-HT(1A) receptor activation inhibits the firing activity of dorsal hippocampus CA(3) pyramidal neurons, the degree of disinhibition produced by the selective 5-HT(1A) receptor antagonist WAY 100635 was determined to assess the net change in 5-HT neurotransmission. Intravenous injection of WAY 100635 did not disinhibit CA(3) pyramidal neuron firing in rats given saline, CP-96,345 for 2 days, or CP-96,344 for 14 days, but produced a significant enhancement of firing in rats treated with CP-96,345 for 2 weeks. Therefore, only long-term treatment with CP-96,345 enhanced the tonic activation of postsynaptic 5-HT(1A) receptors. CONCLUSIONS: Similar to all other major types of antidepressant treatments, these data indicate that substance P antagonists might alleviate anxiety and major depression, at least in part, by enhancing the degree of activation of some 5-HT receptors in the forebrain.
Posted by linkadge on December 11, 2006, at 11:33:25
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by medievil on December 11, 2006, at 11:02:08
This article says that substance P inhibitors affect the release of serotonin, it doesn't say that substance p is involved in the regulation of tollerance to SSRI medications.
Theory and practice are two different things. In theory, NMDA antagonists prevent tollerance to stimulants, but in practice I havn't seen too many people saying it works.
Linkadge
Posted by medievil on December 11, 2006, at 11:37:38
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by linkadge on December 11, 2006, at 11:33:25
actually ive seen many ppl reporting nmda antagonists work for tolerance
Posted by linkadge on December 11, 2006, at 14:59:39
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by medievil on December 11, 2006, at 11:37:38
If it works for you, then go with it.
It also depends on what you are asking for. For instance with opiates or stimulants, one might be able to sustain the theraputic effect of the drugs, but I have never seen anyone claim to be able to sustain the subjective well being that these drugs cause. Ie, I don't think hypomania, or euphoria are sustainable. People have been trying to sustain that since the dawn of time.
Linkadge
Posted by elanor roosevelt on December 11, 2006, at 21:09:46
In reply to Re: neurotransmitter tolerance/poop out downregula, posted by linkadge on December 11, 2006, at 14:59:39
I don't think that people are looking to sustain hypomania or euphoria -- just trying to buy time on the same meds without having to change so often.
This is the end of the thread.
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