title: [Peculiarities of hypnotic effect and pharmacokinetics of hemisuccinate 3-hydroxyphenazepam (levana)].
abstract: The pharmacodynamics and pharmacokinetics of hemisuccinate 3-hydroxyphenazepam (HS-3-HPh, levana)--a new hypnotic 1,4-benzodiazepine derivative--have been studied. It is established that HS-3-HPh in doses of 0.05, 0.1 and 2 mg/kg produces reliable hypnotic action (shortens the period of falling asleep, reduces the number of awakenings at night-time, and increases sleep duration) in the hexenal sleep potentiation test on mice. After a 7-day drug administration, no withdrawal syndrome has been observed. The concentration of 3-oxyphenazepam (3-OP, the main metabolite of HS-3-HPh) in brain after drug administration is significantly higher than the content of 3-OP upon its introduction. The content of 3-OP upon its introduction rapidly decreases, while that upon the administration of HS-3-HPh is retained on a stationary level for a rather long time (about 6 h). It can be suggested that a specific character of HS-3-HPh hypnotic action is determined by peculiarities of its pharmacokinetics, namely, easier entering the brain and subsequent hydrolysis with release of the active metabolite (3-OP).
authors.forename: T A
authors.initials: TA
authors.lastname: Voronina
authors.forename: V B
authors.initials: VB
authors.lastname: Larionov
authors.forename: N Ia
authors.initials: NIa
authors.lastname: Golovenko
authors.forename: L N
authors.initials: LN
authors.lastname: Nerobkova
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051379:Mice; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C038294:3-hydroxyphenazepam