Minaprine antagonises the serotonergic inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on acetylcholine release.
The serotonin agonist, m-trifluoromethylphenylpiperazine (TFMPP), inhibited the K+-evoked release of [3H]acetylcholine ([3H]ACh) from rat hippocampal synaptosomes. The inhibitory effect of TFMPP was blocked by the non-selective 5-HT1 antagonist, methiothepin, but was not affected by ketanserin, mesulergine or spiperone. The 5-HT3 antagonist, MDL 72222, slightly reversed the inhibitory effect. The antidepressant, minaprine, did not modify the basal release of [3H]ACh but it antagonised the inhibitory effect of TFMPP on the K+-evoked release. The maximal reversal was found at 0.3 microM minaprine. These results suggest that minaprine interacts with heterologous presynaptic 5-HT1B receptors. A new approach is thus opened to the study of the mechanism of action of antidepressant drugs.
Bolanos
F
F
Unité de Pharmacologie Neuro-Immuno-Endocrinienne de l'Institut Pasteur, Paris, France.
Fillion
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D010879:Piperazines; D011724:Pyridazines; D012702:Serotonin Antagonists; C006149:minaprine; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D000109:Acetylcholine; D011188:Potassium