P.1.061 - Clinical differences in response to mianserin and fluvoxamine in depressive patients

Abstract

Serotonin (5-HT, 1 μM) induced an inward current in Xenopus oocytes injected with rat brain mRNA under steady voltage clamp conditions of −60 mV. The 5-HT response was blocked by 0.1 μM mianserin, but neither buspirone, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), trifluoromethylphenyl piperazine (TFMPP), pindolol, propranolol, spiperone, ketanserin nor ICS 205–930 exerted effects, suggesting that the 5-HTIC subtype of 5-HT receptors is involved in the current. The 5-HT-induced current was inhibited by imipramine or desipramine with IC50 values of 60 nM or 20 μM, respectively. The response was also inhibited by setiptilline, maprotiline or amoxapine at a dose of 10 μM. Imipramine at 10 μM had no effect on the acetylcholine (ACh, 1 mM)-induced current response. It has been reported that inositol triphosphate (IP3) formation and intracellular Ca2+ are involved in the 5-HT- as well as ACh-induced current and that intracellular injection of either 50 pmol IP3 or 50 pmol Ca2+ mimics the 5-HT-induced current. The response induced by intracellular injection of either 50 pmol IP3 or 50 pmol Ca2+ was not affected by 10 μM imipramine. It is suggested that imipramine, and perhaps other antidepressant drugs tested, blocks 5-HTIC receptors, subsequently inhibiting the 5-HT-evoked current.