Archives Internationales De Pharmacodynamie Et De Thérapie
Etomidate, R-(+)-ethyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate was found to be a potent, short-acting and safe hypnotic; when given intravenously in single doses to mice, rats, guinea-pigs, rabbits and dogs. In rats of different body weight (50, 100, 200 and 300 g) two injection rates were used (2 sec and 2 min). By rapid iv injection in rats of 200 g etomidate (ED50 equal to 0.57 mg/kg) is about 6 times more potent than methohexital (ED50 equal to 3.51 mg/kg) and 25 times more potent than propanidid and thiopental (ED50's equal to 13.4 mg/kg).
Pharmacological effects of ifenprodil (IP), 4-benzyl-alpha-(p-hydroxyphenyl)-beta-methyl-1-piperidineethanol-L-(+)-tartrate monohydrate (Funai Pharmaceutical), a potential vasodilator, were studied in the dog, rabbit, guinea-pig and mouse. 1) Intravenous administration of IP (0.1 approximately 1 mg/kg) exhibited a continuous fall in blood pressure, an increase in heart rate and an increase in cardiac contractile force in the dog. The depressor and chronotropic effects of IP appeared likewise in the pithed dog, and the depressor responses were slightly more evident in the rabbit.
Effects of ifenprodil tartrate, a potent vasodilator, on the autonomic, peripheral and central nerve system were studied in experimental animals. In isolated vas deferens of guinea pigs, the contraction in response to noradrenaline and sympathetic nerve stimulation was competetively antagonized by ifenprodil 10(-7)--10(-5) M (pA2: 7.69 against noradrenaline). Ifenprodil (50 approximately 1,000 mug/kg i.v.) inhibited the contraction of cat nictitating membrane and dog urinary bladder induced by sympathetic nerve stimulation.
Substituted benzylamide derivatives of amino acylamide (compound A,B,C, & D) were found to be less potent local anaesthetics than lignocaine and procaine. However, the four compounds exhibited sedation without ptosis and reduced spontaneous locomotor activity better than methaqualone. Compound A alone antagonised methylamphetamine induced hypermotor activity. The test compounds potentiated hexobarbitone induced hypnosis. Three compounds antagonised calcium induced stoppage of isolated heart of frog.
Beagles, implanted with cortical and subcortical electrodes, were given etomidate i.v. (1 mg/kg) over a period of 10 sec. The effects on the EEG were compared with those obtained with 7 mg/kg of methohexital. Both compounds induced hypnosis for a duration of approximately 8 min. The EEGs showed a remarkable similarity. Visual inspection of the records as well as power spectrum analysis revealed a sustained theta-activity with underlying fast activity. The configuration of the waves was rather sharp.
In the central nervous system, ZM decreased locomotor activity and potentiated hypnosis of hexobarbital-Na in mice. ZM had little hypothermic action and there were no anticonvulsive effects on chemoconvulsion and electroconvulsion shock. ZM, 3 mg/kg i.v. produced a sleep-like pattern in the spontaneous EEG activity of cat; from 20 to 30 min. after injection, spindle burst-like waves (12-13 Hz) appeared in the cortex and subcortex. These EEG activities were antagonized by atropine sulfate.
Propane-1,2-diol (propylene glycol, PG), considered to be a safe solvent and commonly used as a vehicle in pharmacological and toxicological investigations, showed various neuropsychopharmacological activity in albino mice and rats. In lower concentrations (10-20%), at dose level of 10 ml/kg, PG did not show any significant neuropsychopharmacological activity either by i.p. or p.o. routes. But higher concentrations (50-100%), at same dose level by i.p. route, were found to have moderate to marked effect.