Induction of hepatic propoxyphene N-demethylase and aniline hydroxylase activities resulted following repeated oral administration of 25, 50 and 100 mg d-propoxyphene hydrochloride per kg daily in the mouse over a six-day period. A significant elevation in both enzyme activities was noted after a single dose of propoxyphene (100 mg/kg). A dose-related response characterized the observed induction of each microsomal enzyme activity.
Chronic intracerebroventricular injection of phenobarbital results in the development of tolerance to the depressant effects of the drug. The neurotransmitters involved and the manner in which cerebral neurons adapt to this depressant effect are at present unknown. This study examines whether brain serotonin containing neurons participate in the attenuation of the hypnotic response caused by chronic barbiturate administration.
Our experiments demonstrate that morphine and haloperidol produce two distinct and contrasting behavioral states, which can be thought of as exaggerated, isolated, and simplified forms of organized adaptive behavioral states functioning as components of normal motivated behavior. Haloperidol catalepsy constitutes an organized state in which tonic reactions subserving the maintenance of stable static equilibrium prevail, at the expense of phasic locomotor reactions.
The uricosuric agent, probenecid, when administered prior to systemic administration of pentobarbital led to a decreased latency, to loss of righting reflex and to a potentiation of the duration of hypnosis. This potentiation was dose-related and doses of probenecid below 50 mg/kg (i.p.) were without effect. Pretreatment of rats with sulfinpyrazone, another uricosuric agent, yielded similar results. Pretreatment of animals with probenecid shortened the latency to onset of hypnosis induced by halothane (i.p.) and increased the duration of loss of righting reflex, 3-fold.
Archives Internationales De Pharmacodynamie Et De Thérapie
Metamizol (sodium N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino-methylsulphonate; Dipyrone) a non-narcotic analgesic was tested for hypnotic potentiating effect. Metamizol potentiated the hypnosis induced by pentobarbital, barbital and chloral hydrate. This effect was dose-dependent and was inversely proportional to the duration of the analgesic pretreatment. An augmented hypothermia and competition at drug metabolizing sites seem to be the mechanisms involved in the observed effect.
The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice. Ethanol increased locomotor activity in DBA and BALB mice, but not in C57BL mice. Naltrexone, at a dose of 0.1 mg/kg, antagonized the ethanol-induced increase in locomotion similarly in DBA and BALB mice. The duration of loss of righting reflex was, however, differentially affected in all three strains by naltrexone.
South African Medical Journal = Suid-Afrikaanse Tydskrif Vir Geneeskunde
Etomidate (Hypnomidate; Janssen) 1,25% in sterile water was given rectally on 100 occasions to 50 male Long-Evans rats in doses ranging from 4 mg/kg to 12 mg/kg. The onset and duration of ataxia and hypnosis (i.e. loss of righting ability) were recorded. Ataxia was observed in all rats, even at the lowest dose levels. The lowest hypnotic dose was 6 mg/kg, when 2 out of 5 rats lost their righting ability. In all 50 rats given 8 mg/kg or more hypnosis occurred within 4 minutes (range 2-4 minutes, average 3,3 minutes), from which they recovered within an average of 10,4 minutes.