title: A comparison of the anticonvulsant effects of competitive and non-competitive antagonists of the N-methyl-D-aspartate receptor.
abstract: The anticonvulsant activity of two competitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, 2-amino-7-phosphonoheptanoic acid (APH) and 3-[2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP), and two non-competitive NMDA antagonists, phencyclidine (PCP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), were compared in 4 models of induced seizures in mice. All 4 drugs protected against tonic extensor seizures induced by pentylenetetrazol (PTZ), by submaximal (15 mA) electroconvulsive shock (ECS) and by maximal (50 mA) ECS. Similar orders of potency (i.e., MK-801 greater than PCP greater than or equal to CPP greater than APH) were seen in each of the 3 seizure models. All 4 drugs failed to block clonic seizures induced by picrotoxin in the dose ranges that protected from tonic seizures. These data are consistent with other data demonstrating that competitive and non-competitive NMDA antagonists have similar pharmacologic effects. These results also support the suggestion that the anticonvulsant effects of competitive and non-competitive NMDA antagonists are mediated by the NMDA receptor-ionophore complex.
authors.affiliation: Department of Central Nervous System Diseases Research, G. D. Searle & Co., IL 60077.
authors.forename: M E
authors.initials: ME
authors.lastname: Nevins
authors.forename: S M
authors.initials: SM
authors.lastname: Arnolde
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010622:Phencyclidine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000596:Amino Acids; D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D010622:Phencyclidine; C031231:2-amino-7-phosphonoheptanoic acid; D010433:Pentylenetetrazole