Modulation of release of acetylcholine from the striatum by a proposed excitatory amino acid antagonist U-54494A: comparison with known antagonists, diazepam and phenytoin.
The effect of (U-54494A) cis-3,4-dichloro-N-methyl-N-[2-(1-Pyrrolidinyl)- cyclohexyl] benzamide monohydrochloride, an excitatory amino acid antagonist, on N-methyl-D-aspartic acid (NMDA)- and K(+)-evoked release of [3H]acetylcholine [( 3H]ACh) from slices of striatum was investigated. For the purpose of comparison, MK 801, PCP, CGP 37849, CPP, phenytoin and diazepam were investigated under identical conditions. Both U-54494A and the excitatory amino acid antagonists blocked NMDA-evoked release of [3H]ACh but these compounds failed to inhibit K(+)-evoked release of this neurotransmitter. Phenytoin blocked both NMDA and K(+)-evoked release of [3H]ACh, whereas diazepam was ineffective under similar conditions. These observations indicate that excitatory amino acid antagonists, including U-54494A, may mediate their anticonvulsant effect by blocking the activity of NMDA receptors, diazepam by activating the benzodiazepine receptors and phenytoin by inhibiting the activity of various depolarizing agents.
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CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats
D000927:Anticonvulsants; D011759:Pyrrolidines; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D010672:Phenytoin; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C054216:U 54494A; D010622:Phencyclidine; D000109:Acetylcholine; D003975:Diazepam; D011188:Potassium