Posted by PeterJ on May 18, 2000, at 3:53:39
In reply to Re: SSRIs: - Different (Peter), posted by Cam W. on May 18, 2000, at 2:13:48
> I have found that you can be burned by in vitro receptor binding information. If it were entirely accurate, then Effexor would bs strictly an SSRI, with mild norepinephrine side effects (at least a 1000-fold difference in k-values). This is not the case, as many people experience significant norepinephrine efficacy with Effexor.
Actually, Venlafaxine is one case in which the Ki values match the clinical effects pretty well. The Ki values for serotonin reuptake versus norepineprhine differ by a factor of 5.4 (more potent at serotonin sites) according to Richelson. A study just out by Preskorn's group in the Archives of General Pyschiatry shows that effects on human subjects are primarily serotonergic at 75mg/day, with pronounced noradrenergic effects occuring at 375mg/day.
Blier and DeMontigny's group (up your way at McGill) do claim some discrepencies in rat studies of raphe vs locus ceruleus effects compared to receptor binding, but even they find ratio of 3, which isn't too far from the clinically observed effects.
1. Richelson, Elliott. Synaptic Effect of Antidepressants. J Clin Psychopharm. Vol 16, No. 3, Suppl. 2. June 1996 1S-9S.
2. Harvey, Ann; Rudolph, Richard; Preskorn, Sheldon. Evidence of the Dual Mechanisms of Action of Venlafaxine. Arch Gen Psychiatry. Vol 57, May 2000, 503-509
3. Beique JC; de Montigny C; Blier P; Debonnel G. Venlafaxine: discrepancy between in vivo 5-HT and NE reuptake blockade and affinity for reuptake sites. Synapse 1999 Jun 1;32(3):198-211
Nonetheless I agree with your point that receptor binding information has to be taken with a grain of salt. That's why I am looking for people's clinical reactions as a guide to what really goes on.
> Interesting thread here. Good luck with the Celexa - CamThanks, I appreciate your interest, and I'm keeping my fingers crossed on the Celexa.
Peter
poster:PeterJ
thread:33808
URL: http://www.dr-bob.org/babble/20000517/msgs/33867.html