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.
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