In Vivo and in Vitro Studies on a Muscarinic Presynaptic Antagonist and Postsynaptic Agonist: BM-5
The oxotremorine analog, compound BM-5: N-methyl-N(1-methyl-4-pyrrolidino-2-butynyl)acetamide (11) (Fig. 1) has been studied with respect to its muscarinic actions (9, 11). Jenden and colleagues found that the compound inhibited oxotremorine induced tremor in mice (11) while it was a partial agonist producing contraction of the ileum (9, 11). In parallel studies we found that compound BM-5 behaved as a presynaptic antagonist enhancing the evoked release of acetylcholine from the myenteric plexus and from synaptosomes prepared from rat hippocampus (9). In other presumable postsynaptic tests, such as the atropine sensitive stimulation of cyclic 3’5’guanosine monophosphate (cGMP) synthesis in human lymphocytes — a noninnervated “postsynaptic model tissue” — or inhippocampal slices, compound BM-5 behaved as a muscarinic agonist since it enhanced cGMP synthesis (9).
KeywordsMuscarinic Receptor Myenteric Plexus Memory Consolidation Guanosine Monophosphate Muscarinic Agonist
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