Posted by linkadge on November 7, 2007, at 14:13:52
In reply to Re: Dopamine agonists cause sedation. But why?? » linkadge, posted by Astounder on November 3, 2007, at 12:44:09
>Furthmore, it may be that stimulation of the 5->HT1a receptor partially antagonizes the >hyperthermia from 5-HT2a stimulation. The >selective 5-HT1a full agonist 8-OH-DPAT induces >hypothermia that is blocked by a 5-HT1a >antagonist.
This is essentially what I am referring to. Excessive 5-ht1a agonism can cause hypothermia.
>So it makes sense drugs that block 5-HT1a >significantly like cyproheptadine & >chlorpromazine are not as effective in reducing >the hyperthermia.
Cyproheptadine is still much stronger at 5-ht2 than 5-ht1a. (At least according to the PDSP).
>Ritanserin is highly selective for 5-HT2a over 5->HT1a. Look at the binding data:
But what I mean is that other receptors may be involved. Lithium for instance can sometimes cause serotonin synrdrome when combined with SSRI's or MAOI's. Lithium has no direct effect on 5-ht1a or 2a, but does have affinity for 5-ht1b.
So its not necessarily right to conclude that 5-h2a receptors are solely responsible for ritanserin's anti SS effects. Ie other receptors may be involved.>They're not case studies; they were active drug >controlled clinical studies with 60 and 30 >patients. The patients were not selected on the >grounds of being treatment resistant; in fact >the pilot study included dysthymics.
I don't think you know what I am referring to. I will try to find the reference.
>I can't find any case studies of serotonin syndrome resulting from the sole combination of amitriptyline and a MAOI, whereas there's plenty for MAOIs and other drugs that significantly block serotonin reuptake.
Amitryptaline is still a potent SSRI. Next to clomipramine, and perhaps doxpine, amitryptaline is one of the more potent serotinin acticing TCA's.
>Clomipramine and imipramine are the only >significantly serotonergic tricyclics other than >amitriptyline. One major difference between >clomipramine, imipramine, and amitriptyline is >potency at the 5-HT2a receptor. According to >this review, tricyclics do not produce the >serotonin syndrome, other than clomipramine and >imipramine:
Yes, but unlike imipramine, clomipramine *is* a potent 5-ht2a antagonist.
>I was writing a long rebuttal, but this study >stopped me:
>The only drugs that are definitely known to >cause cardiac fibrosis are direct 5-HT2b >agonists, though SERT knockout mice display >valvulopathy, so obviously SERT can be involved >in the etiology.
Thats what I was going to refer to. SERT knockout mice have some interesting cardiac issues. Remember, you wouldn't get GI upset if serotonin wasn't being functionally increased at receptors in the perihpery. My guess is that while SSRI's are not potent direct agonists, they could still lead to such chences over longer periods. It seems to be a dose pependant issue. Drugs like mirapex *are* linked to some of such cardiac changes, but to a lesser degree. Mirapex is less potent as a 5-ht2b agonist than the withdrawn drugs.
Drugs like the TCA's might not have such issues as many have antagonistic propeties at 5-ht2b.
Linkadge
poster:linkadge
thread:791344
URL: http://www.dr-bob.org/babble/20071104/msgs/793770.html