Archives internationales de pharmacodynamie et de thérapie
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Arch Int Pharmacodyn Ther · Mar 1987
Comparative StudyGastrointestinal transit following intrathecal or subcutaneous narcotic analgesics.
This paper reports investigations on the effects on gastrointestinal transit of subcutaneous or intrathecal administration of opiates: morphine, sufentanil and alfentanil. Subcutaneous administration of opiates produced a significant dose-dependent decrease in transit of a charcoal meal test. ⋯ In addition, sufentanil and alfentanil, on intrathecal administration in rats with chronically implanted catheters, caused a marked dose-dependent slowing of the passage of meal. Prior s.c. administration of the opiate antagonist naloxone completely blocked the depression of gastrointestinal transit caused by high doses of intrathecal sufentanil and s.c. administered morphine.
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Arch Int Pharmacodyn Ther · Nov 1984
Effects of celiprolol (REV 5320), a new cardioselective beta-adrenoceptor antagonist, on in vitro adenylate cyclase, alpha- and beta-adrenergic receptor binding and lipolysis.
Celiprolol has been previously shown in vivo to be an effective beta-adrenergic antagonist with cardio-selectivity and weak intrinsic sympathomimetic activity but no membrane stabilizing or "quinidine-like" effects. With in vitro systems reported here, the following was observed. Against the stimulation of adenylate cyclase from dog ventricular muscle by isoproterenol, celiprolol had a Ki of 2.6 X 10(-7) M which was about 1/20 the potency of propranolol. ⋯ Celiprolol inhibited isoproterenol-induced lipolysis with a potency about 2 times greater than practolol. Unlike propranolol, celiprolol at very high concentrations did not show non-specific inhibition of lipolysis induced with cyclic nucleotides. These and other published data would suggest the following: in vitro beta adrenergic receptor antagonist activity can be demonstrated for celiprolol, cardioselectivity is due to a combination of many factors including stereochemistry of the molecule and in vivo distribution and metabolism, celiprolol does not possess "non-specific" membrane activity, the "intrinsic-sympathomimetic activity" of celiprolol is selectively observed in some but not all in vitro test models, celiprolol has about a 10-fold selectivity for alpha 2-vs. alpha 1-receptors which is relatively unique to beta-antagonists and needs further investigations as to the potential physiological significance.
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Arch Int Pharmacodyn Ther · May 1982
Effects of alpha-adrenoceptor antagonists administered intraventricularly on central hypotensive action of clonidine and on central hypertensive action of methoxamine in rabbits.
In urethane-anesthetized rabbits blood pressure was lowered by intraventricular clonidine (30 microgram) and increased by intraventricular methoxamine (1 mg). Clonidine is well known to cause hypotension by acting on central alpha-adrenoceptors. The hypertensive effect of intraventricular methoxamine was not observed in cord-sectioned rabbits, in guanethidine-treated adrenalectomized rabbits and in phentolamine-treated rabbits, indicating the effect was central in origin. ⋯ Pretreatment with 2 mg of labetalol inhibited the methoxamine effect but was ineffective against clonidine. Pretreatment with 500 microgram of phentolamine was effective in antagonizing the clonidine effect but twice the dose was needed to inhibit the methoxamine effect. From the findings that the hypertensive effect of methoxamine and the hypotensive effect of clonidine were inhibited differently by various alpha-adrenoceptor antagonists and that the selectivity of these antagonists for the methoxamine and clonidine effect is similar, respectively, to that for alpha 1- and alpha 2-adrenoceptors in the peripheral tissues, we concluded that the methoxamine hypertension and the clonidine hypotension are due to the stimulation of alpha 1- and alpha 2- adrenoceptors in the brain, respectively.
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Arch Int Pharmacodyn Ther · Mar 1982
Postnatal development and behavior in offspring of enflurane exposed pregnant rats.
Sperm positive (day zero gestation) Fischer 344 rats were exposed to air or to 1500 ppm enflurane by inhalation for 6 hr a day for 21 consecutive days. Enflurane exposed females and their controls were allowed to deliver and raise their offspring. ⋯ Sex differences were seen in many parameters as expected, but statistically significant treatment related effects were observed only in the food maze learning behavior and in the pentobarbital sleeping time in the puberty aged male offspring. From our data we can conclude that offspring of pregnant female rats exposed to enflurane at 1500 ppm throughout gestation show minimal, if any, significant clinical or behavioral pathological effects.
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Arch Int Pharmacodyn Ther · Jun 1981
The anti-inflammatory, analgesic and antipyretic activities of non-narcotic analgesic drug mixtures in rats.
The effects of non-narcotic analgesics have been examined, separately and in admixture, on carrageenan-induced hind paw oedema and on yeast-induced hyperalgesia and hyperthermia in adult rats. The efficacy of the drugs was evaluated using the kinetics of drug-receptor interaction. In addition, the hypothesis was tested that the anti-inflammatory, analgesic and antipyretic activities of the drug mixtures used equal the addition of the activities of the individual drugs and could be predicted from their intrinsic activities and affinities. ⋯ Incidentally, at some of the higher dose levels potentiation of the activity of the drugs was found. Low doses of the triple combinations: aspirin + paracetamol + caffeine and aspirin + phenacetin + caffeine showed anti-inflammatory and antipyretic activities which were not different from those expected on the basis of addition, but the activities observed with higher doses of these combinations indicated potentiation. It is concluded that, in the rat, the anti-inflammatory, analgesic and antipyretic activities of dual and triple combinations of aspirin, paracetamol, phenacetin and caffeine at least equal the activities expected on the basis of addition.