Posted by linkadge on November 2, 2007, at 15:08:36
In reply to Re: Dopamine agonists cause sedation. But why?? » amigan, posted by Astounder on November 2, 2007, at 12:43:49
>The most potent 5-HT2a blocking antidepressant >is the tricyclic amitripytline (Elavil). It has >higher affinity than serotonin itself, which >explains why, even though a highly effective >serotonin and norepinephrine reuptake inhibitor, >it does not cause the serotonin syndrome in >combination with a full MAOI
That depends. It is not a strong 5-ht1a antagonist which means that some symptoms of serotonin syndrome can still occur namely hyothermaia.
>Again, cyproheptadine and Elavil bind strongly, >with Elavil acting as an inverse agonist. The >pipeline antidepressant/anti-insomnic drug >agomelatine (Valdoxan) is selective for 5-HT2c >receptors in addition to M1 & M2 melatonin >receptors.
The combination of cyproheptadine and melatonin is very effective for insomnia in myself.
>Conversely, blockers of the 5-HT2 receptors also >result in their downregulation.
Probably by indireclty potentiating 5-ht1a
>I would stay away from 5-HT2c antagonists >honestly, unless you're OCD or anorexic, since >they can cause massive weight gain. If you work >out though, they can help in bulking up.
For some people agents with 5-ht2c antagonism can be very effective for reducing agitation and augmenting antidepressant responce. Fluoxetine for example is actually a stronger 5-ht2c antagonist that 5-ht reuptake inhibitor. Unlike other SSRI's, fluoxetine actually increase frontal cortex levels of nor/dopamine.
>Drugs with stimulate these receptors are not >always anxiogenic: MDMA's psychomotor >stimulating & wakefulness promoting effects are >partly through 5-HT2a stimulation, and this >receptor may play a part in MDMA's release of >oxytocin (which is responsible for its >anxiolytic, empathogenic, and disinhibiting >effects).
MDMA is not a selctive 5-ht2a agonist though. Its hard to say whether it is these metabolites are really non anxiogenic, or if other aspects of the drug simply cancel out the anxiogenic effects of 5-ht2a agonist metabilites. Trazodone, for instance, has a metabolite that mcpp which is similar in some respects to MDMA. MCPP is a 5-ht2a agonist, yet trazodone itself is a 5-ht2a antagonist.
Also, MDMA or one of its metabolites acts as a 5-ht2c antagonist which probably enhnaces accumbal release of dopamine.
>Stimulation of the 5-HT2c receptor is >responsible for the actions of the serotonergic >anorectics, like megadose (900 mg/d) 5-HTP, >reuptake inhibitors like sibutramine, and >releasers like fenfluramine.
Yeah and 5-ht2b agonsts are what is responsible for cardiac hypertrophy and valve dammage. Probably why to avoid all SSRI's.
>opiate abuse has been known to cause weight >loss, though withdrawal can cause weight gain.
Or the exact opposite.
>This is probably because opiates substitute for >food-induced reward in animal studies.
Animals will not starve themselves to death if able to continuasly self administer opiates as they will if they are able to continusly self administer cocaine/meth.
Linkadge
poster:linkadge
thread:791344
URL: http://www.dr-bob.org/babble/20071027/msgs/792990.html