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DuP 996 (3,3‐bis(4‐pyrindinylmethyl)‐1‐phenylindolin‐2‐one) enhances the stimulus‐induced release of acetylcholine from rat brain in vitro and in vivo
Author(s) -
Nickolson Victor J.,
William Tam S.,
Myers Melvin J.,
Cook Leonard
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430190307
Subject(s) - acetylcholine , chemistry , cholinergic , medicine , muscarinic acetylcholine receptor , endocrinology , cerebral cortex , cholinergic neuron , pharmacology , biology , biochemistry , receptor
DuP 996, in micromolar concentrations, enhances the K + ‐stimulated release of acetylcholine (ACh) in rat cerebral cortex, hippocampus, and caudate nucleus slices in vitro, without effect on basal release. DuP 996 has very weak affinity for rat brain muscarinic or nicotinic receptors and does not inhibit acetylcholinesterase activity of rat brain. Upon subcutaneous administration, DuP 996, in doses of 0.1 to 1 mg/kg, increase the output of ACh from the cerebral cortex of awake, freely moving rats. In the mouse, scopolamine‐induced hyperactivity is reduced by DuP 996 in doses of 0.3–0.5 mg/kg (s.c.). In addition, pancuronium HBr‐induced neuromuscular blockade is reversed by DuP 996 (ED 50 = 1.7 mg/kg s.c.). The enhancement by DuP 996 of K + ‐stimulated transmitter release is not limited to the cholinergic system but is also observed in the dopaminergic system in the rat caudate nucleus and in serotonergic systems. K + ‐stimulated release of gamma‐aminobutyric acid and glutamic acid in rat cerebral cortex, however, is only slightly enchanced by DuP 996, whereas no effects are observed on K + ‐stimulated release of cortical norepinephrine. DuP 996 may have therapeutic value in the treatment of diseases involving chlinergic and minoaminergic deterioration, like Alzheimer's Disease.