(-)-Propranolol and (+/-)-cyanopindolol are mixed agonists-antagonists at serotonin autoreceptors in the hippocampus of the rat brain.
The effects of (-)-propranolol, (+)-propranolol and (+/-)-cyanopindolol on the release of [3H]5-hydroxytryptamine [( 3H]5-HT) were investigated in synaptosomes from the hippocampus of the rat, depolarized in superfusion with 15 mM KCl. (-)-Propranolol, but not (+)-propranolol, inhibited in a concentration-dependent way the K+-evoked release of [3H]5-HT. (+/-)-Cyanopindolol behaved similarly but was about 10 times more potent than (-)-propranolol. The inhibitory effects of (-)-propranolol and (+/-)-cyanopindolol were prevented by the autoreceptor antagonist methiothepin. Both beta-adrenoceptor antagonists antagonized the inhibition by exogenous 5-HT of the K+-evoked release of [3H]5-HT. The data suggest that some beta-adrenoceptor antagonists may behave as mixed agonists-antagonists at the 5-HT autoreceptor. Synaptosomes in superfusion appear to be particularly suitable to study separately agonistic compared to antagonistic activity of compounds having a mixed agonist-antagonist profile.
D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013237:Stereoisomerism; D013574:Synaptosomes / Q000378:metabolism
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C047975:cyanopindolol; D011433:Propranolol; D010869:Pindolol; D011188:Potassium