Posted by Cam W. on May 18, 2000, at 16:00:23
In reply to Re: SSRIs: - Different (Cam), posted by PeterJ on May 18, 2000, at 3:53:39
Peter - Thanks for keeping me honest. My memory isn't what it used to be. I checked my files at work and the 1000 figure came from Tatsumi, et al (Richelson's group, 1997) study, but was the 5HT/DA transporter selectivity factor rather than the 5HT/NE transporter selectivity factor of 120. The Kd's of 5HT & NE transporters in vitro were 8.9nM and 1060nM, respectively.Tatsumi, et al, Pharmacological profile of antidepressants and related compounds at human monoamine transporters, Eur J Psychopharmacology, 340(1997): 249-258.
Inhibition constants (Ki) from an Owens, et al (Nemeroff's group, 1997) study gave a similiar 100:1 ratio in cultured human cells (5HT - 102nmol/L; NE - 1644nmol/L).
Owens, MJ, et al, Neurotransmitter receptor and transporter binding profiles of antidepressants and their metabolites, J Pharmacol and Exp Ther, 283(1997): 1305-1322.
So, since I do not have access to the Richelson study you mention, I decided to check in Preskorn's book and look at the charts for Ki's. His charts, while not giving exact values, seem closer to your value of 5.4 than the value of 100 (for the selectivity factor) in Richelson's 1997 Kd study. Since comparing dissociation constants (Kd) and inhibition constants (Ki) may be different (are they?), it may be we are comparing apples and oranges. (I've been out of school too long to remember the difference).
Preskorn S, Outpatient management of depression: aguide for the primary care practioner, Chapter 6: The rational basis for the development and use of newer antidepressants, PCS, 1999.
The Harvey study you mention is in vivo, but the are measuring transporter levels outside of the CNS. Even that the pressor (NE) response at day 15 was not statistically significant in low and high dose venlafaxine groups (p 505-506). This is surprizing, as clinical experience shows that venlafaxine does have NE action at higher doses, as seen with the escalating dose/response curve.
Thanks again for finding my mistake. I am really not able to dig this deep into these subjects, anymore. This was fun and shows that I still make mistakes. Keep on Babbling, your presence here is needed to keep us honest. Also, good luck with your Celexa.
Fellow Babbler - Cam
poster:Cam W.
thread:33808
URL: http://www.dr-bob.org/babble/20000517/msgs/33920.html