title: Mildronate exerts acute anticonvulsant and antihypnotic effects.
abstract: The effects of mildronate [3-(2,2,2-trimethylhydrazinium) propionate], an inhibitor of L-carnitine biosynthesis and an anti-ischaemic drug, were examined in various in-vivo conditions to investigate the neuropharmacological profile after acute administration. Mildronate (200 mg/kg, acute intraperitoneal administration) exerted anticonvulsant activity in a chemoconvulsant pentylenetetrazole-induced clonic and tonic seizure test but did not change the effects of a convulsion-inducing dose of (+)-bicuculline, a gamma-aminobutyric acid receptor antagonist. Mildronate also dose-dependently inhibited the sleeping time in ethanol-induced loss of righting reflex test. However, in a pentylenetetrazole-induced seizure test, mildronate significantly stimulated the anticonvulsant activity of ethanol. The anticonvulsant activity of mildronate was completely blocked after pre-treatment with alpha2-adrenergic receptor antagonist yohimbine (2 mg/kg) and nitric oxide synthase inhibitor N(G)-nitro-L-arginine (10 mg/kg). These results show that the acute administration of mildronate induces anticonvulsant and antihypnotic effects, which involve alpha2-adrenergic receptor and nitric oxide -dependent mechanisms. These findings indicate that the acute administration of mildronate could be beneficial for the treatment of seizures and alcohol intoxication.
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia. liga@biomed.lu
authors.forename: Liga
authors.initials: L
authors.lastname: Zvejniece
authors.forename: Baiba
authors.initials: B
authors.lastname: Svalbe
authors.forename: Marina
authors.initials: M
authors.lastname: Makrecka
authors.forename: Edgars
authors.initials: E
authors.lastname: Liepinsh
authors.forename: Ivars
authors.initials: I
authors.lastname: Kalvinsh
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
mesh_terms: D000435:Alcoholic Intoxication / Q000188:drug therapy; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D008763:Methylhydrazines / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy*; D012890:Sleep / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D008763:Methylhydrazines; D018341:Receptors, Adrenergic, alpha-2; D009569:Nitric Oxide; D000431:Ethanol; C050147:3-(2,2,2-trimethylhydrazine)propionate