MPEP, an antagonist of metabotropic glutamate receptors, exhibits anticonvulsant action in immature rats without a serious impairment of motor performance.
An antagonist of type I metabotropic glutamate receptors MPEP was found to exhibit anticonvulsant action in adult rodents. Present experiments were focused on action of this drug against pentetrazol-induced motor seizures in immature rats 12-, 18- and 25-days old. Dose of pentetrazol (100 mg/kg s.c.) was chosen to elicit minimal clonic seizures and (after a longer latency) generalized tonic-clonic seizures. Pretreatment with MPEP (doses from 10 to 80 mg/kg i.p.) resulted in a dose-dependent suppression of the tonic phase of generalized tonic-clonic seizures in all age groups studied. Efficacy of MPEP was higher and the effect lasted longer in 12- than in 25-day-old rats. In addition, minimal clonic seizures were suppressed in 18-day-old rats. Motor abilities of immature animals were not compromised by MPEP in doses of 20 and/or 40 mg/kg i.p., only righting reflex was a little slowed down in 12- and 18-day-old rats. In contrast to antagonists of ionotropic glutamate receptors anticonvulsant doses of MPEP do not induce unwanted side effects in motor performance of developing rats.
Mares
Pavel
P
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic. maresp@biomed.cas.cz
Mikulecká
Anna
A
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000517:prevention & control; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000517:prevention & control; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects
D000927:Anticonvulsants; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; D010433:Pentylenetetrazole