Agonist and antagonist actions of (-)pindolol at recombinant, human serotonin1A (5-HT1A) receptors.
It has been proposed that the arylalkylamine, (-)pindolol, potentiates the therapeutic action of antidepressant drugs in humans by blockade of 5-HT1A autoreceptors. Its interactions at human 5-HT1A receptors have not, however, been directly characterized. Herein, we demonstrate that (-)pindolol exhibits nanomolar affinity at human 5-HT1A receptors expressed in Chinese Hamster Ovary cells (CHO-h5-HT1A; Ki = 6.4 nmol/L). In a functional test of receptor-mediated G-protein activation (stimulation of [35S]-GTP gamma S binding) (-)pindolol displays an efficacy of 20.3% relative to the endogenous agonist, 5-HT (= 100%). (-)Pindolol also antagonizes 5-HT (100 nmol/L)-stimulated [35S]-GTP gamma S binding, reducing it to 19.8% of control binding. These data indicate that (-)pindolol acts as a (weak) partial agonist at CHO-h5-HT1A receptors and that it blocks the action of 5-HT at these sites.
Newman-Tancredi
A
A
Department of Psychopharmacology, Institut de Recherches Servier, Paris, France.
Chaput
C
C
Gavaudan
S
S
Verrièle
L
L
Millan
M J
MJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D010869:Pindolol / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D019204:GTP-Binding Proteins; D010869:Pindolol; D010879:Piperazines; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C081293:WAY 100135