Possible anticonvulsant action of nifedipine against two chemically-induced convulsions

In this investigation, two sets of experiments were carried out to assess the possible anticonvulsant action of nifedipine. The nifedipine was tested after the induction of convulsions by pentylenetetrazol[PTZ] and strychnine [ST]. In the first set of experiments, four groups of albino mice were given PTZ in a dose of 100 mg/kg, 15 and 30 minutes following the ip injection of saline, 5 mg/kg of phenytoin, 30 mg/kg of nifedipine and 45 mg/kg of nifedipine. The second set of experiments was dealt with in the same way as the first one except that the convulsions in this time were induced by ip administration of strychnine in a dose of 1 mg/kg. The results revealed that the ip administration of phenytoin into mice 5 mg/kg] 15 minutes before PTZ produced no significant change in the onset of PTZ action, the time of peak PTZ effect and the mean survival time [MST] of mice. The ip administration of nifedipine into mice in its two selected dose levels, 30 and 45 mg/kg, 30 minutes before PTZ injection caused significant increases in the onset of PTZ action, the time of peak convulsive effect of PTZ as well as the MST of mice. Against- strychnine-induced convulsions, the ip injection of phenytoin [5 mg/kg] into mice proved to prolong the MST of animals only if this drug was given 30 minutes before strychnine

interrelationships between dieldrin, intestinal active transport and mucosal cyclic AMP concentrations

The effect of dieldrin on the intestinal transport of actively transported non-electrolytes and intestinal mucosal cyclic AMP concentrations was evaluated in the isolated rat jejunum and ileum. Certain dose and concentration levels of dieldrin were found to be capable for enhancing the intestinal active transport of D-glucose and L-leucine. This enhancement in the active transport of non-electrolytes by dieldrin was paralled by an increase in the mucosal cyclic AMP concentrations in both preparations. There was a positive correlation between mucosal cyclic AMP concentrations and the active transport of D-glucose and L-leucine in the isolated jejunum and ileum of rat as indication by investigating the effect of dieldrin in combiution with either forskolin or 3-isobutyl-l-methy-Lxanthine [IBMX]. on these parameters. It is suggested that cyclic AMP may act as a mediator for the enhancement effect of dieldrin on the intestinal active transport of non-electrolytes

myoneural effects of verapamil on the rat phrenic nerve-diaphragm preparation

The effects of verapamil on the neuromuscular transmission and muscular contraction were studied using isolated phrenic nerve diaphragm preparation. The diaphragmatic contractions elicited by either indirect or direct electrical stimulation were inhibited by verapamil. The inhibitory effect of verapamil was greater with indirect than direct stimulation. Verapamil was found to be capable to enhance the paralysis of the indirectly stimulated rat diaphragm induced by either d-tubocurarine or succinylcholine. The combination of verapamil and d-tubocurarine- led to a synergistic inhibition of the neuromuscular transmission, while the combination of verapamil and succinylcholine led to additive inhibition. Pretreatment with verapamil abolished and markedly inhibited the stimulant effects of digoxin on the indirectly and directly induced diaphragmatic -contractions respectively. Doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of verapamil on either indirectly or directly elicited diaphragmatic contractions. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly, while pretreatment with adenosine enhanced the inhibitory effect of verapamil on diaphragmatic contractions elicited by indirect electrical stimulation. The enhancement effects of aminophylline and forskolin on the contractions of rat diaphragm induced either indirectly or directly were abolished and markedly inhibited respectively by pretreatment with verapamil. Pretreatment with verapamil markedly inhibited the enhancement effect of caffeine on diaphragmatic contractions induced indirectly, but did not change the enhancement effect of caffeine on directly induced contractions. It is concluded that verapamil acts by a -mixture of pre-and postsynaptic effects to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction

Disturbance in the pressor and chronotropic effects of epinephrine and norepinephrine as well as in the function and structure of adrenal cortex induced by O,P'-DDt

The effect of O, P'-DDT on the cardiovascular effects of catecholamines and on the function and structure of the adrenal cortex was evaluated in rabbits. Administration of 50 mg/kg/day O, P'-DDT orally to rabbits for two and three weeks significantly decreased the mean arterial blood pressure and heart rate. The mean percentage increase in the pressor and chronotropic effects of intravenously injected graded doses of epinephrine and norepinephrine were markedly decreased in vagotomized rabbits pretreated with 50 mg/kg/day O, P'-DDT orally for two and three weeks. These effects of O,P'-DDT were more marked after three weeks than after two weeks of its administration. The administration of cortisol, but not aldosterone was found to be capable of potentiating the pressor and chronotropic effects of intravenously injected graded doses of catecholamines in vagotomized rabbits pretreated with O,P'-DDT. Treatment of rabbits with 50 mg/kg/day O,P'-DDT orally for one week produced insignificant change in the plasma cortisol level, significant decrease in the plasma aldosterone and sodium levels and significant increase in the plasma potassium level. The plasma cortisol, aldosterone and sodium levels were markedly decreased, while the plasma potassium level was markedly increased after administration of the same dose of O, P'-DDT to rabbits for two and three weeks. Also, the intensity of these effects of O, P'-DDT was directly related to the duration of administration. The administration of ACTH to rabbits pretreated with 50 mg/kg/day O,P'-DDT orally for three weeks, failed to alter the effects of O,P'- DDT on the plasma cortisol aldosterone and electrolyte levels. The histopathological changes were studied and indicated that O,P'-DDT has a definite effect on the adrenal cortex of the rabbits ranging from outer zonal fatty change to diffuse fatty change with hemorrhage and foci of necrosis depending on the duration of administration. It is concluded that O,P' DDT has the ability to produce a disturbance in the cardiovascular effects of catecholamines and a direct impairment in the function and structure of the adrenal cortex