Effects of NNC 711, a GABA uptake inhibitor, on pentylenetetrazol-induced seizures in developing and adult rats.
The anticonvulsant action of NNC 711 [(1-(2-((diphenylmethylene) amino) oxy) ethyl)-1,2,4,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride], an inhibitor of the GABA transporter GAT-1, was studied in a model of pentylenetetrazol-induced motor seizures in rats 7, 12, 18, 25, and 90 days old. NNC 711 at doses of 0.25-20 mg/kg i.p. exhibited two effects in rat pups: a suppression of minimal clonic seizures in age groups in which this type of seizure could be reliably elicited (i.e. in rats aged 18 and 25 days); and a specific suppression or restriction of the tonic phase of generalized tonic-clonic seizures (GTCS) expressed in 18- and especially 12-day-old rats. Effects of NNC 711 on GTCS in 7- and 25-day-old rats were irregular. Adult (i.e. 90-day-old) animals exhibited abolition of generalized tonic-clonic seizures; minimal clonic seizures were suppressed only after substantially higher doses. The abolition of minimal seizures by doses too low to influence generalized tonic-clonic seizures as observed in rat pups is unique among antiepileptic drugs. In addition, an EEG study in rat pups demonstrated dissociation of EEG signs and motor seizures in some animals.
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
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Kubová
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Haugvicová
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Mares
D000375:Aging; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D018756:GABA Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D010091:Oximes / Q000008:administration & dosage / Q000627:therapeutic use*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D000927:Anticonvulsants; D003292:Convulsants; D018756:GABA Antagonists; D009557:Nipecotic Acids; D010091:Oximes; C078793:NNC 711; D010433:Pentylenetetrazole