ORIGINAL ARTICLESMildronate exerts acute anticonvulsant and antihypnotic effectsZvejniece, Ligaa; Svalbe, Baibaa b; Makrecka, Marinaa c; Liepinsh, Edgarsa; Kalvinsh, Ivarsa; Dambrova, MaijaaAuthor Information aLatvian Institute of Organic Synthesis bUniversity of Latvia cRiga Stradins University, Riga, Latvia Correspondence to Dr Liga Zvejniece, PhD, Latvian Institute of Organic Synthesis, Aizkraukles St 21, Riga, LV-1006, Latvia E-mail: [email protected] Received 16 February 2010 Accepted as revised 4 June 2010 Behavioural Pharmacology: September 2010 - Volume 21 - Issue 5-6 - p 548-555 doi: 10.1097/FBP.0b013e32833d5a59 Buy Metrics 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 γ-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 α2-adrenergic receptor antagonist yohimbine (2 mg/kg) and nitric oxide synthase inhibitor NG-nitro-L-arginine (10 mg/kg). These results show that the acute administration of mildronate induces anticonvulsant and antihypnotic effects, which involve α2-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. © 2010 Lippincott Williams & Wilkins, Inc.