Modulation of the antiepileptic activity of sodium valproate by lithium chloride against pentylene-tetrazole and strychnine-indced seizures in mice.

In this study, the influence of lithium chloride [LiCl] in a dose of 10 mg/kg on the anticonvulsant activity of sodium valproate [VAL] in doses of 200 or 600 mg/kg was valuated against both pentylenetetrazol [PTZ; 100 mg/kg] and strychnine [ST; 1 mg/kg]-induced seizures and mortality. The results revealed that the ip administration of VAL alone was effective against seizures and mortality induced by both PTZ and ST. Significant increases in the onset of seizures and the MST as well as the percent of mice protected from death were recorded. In contrast, the administration of LiCl alone significantly reduced the onset of seizures and offered no protection against death caused by the same convulsive agents, PTZ and ST. Compared with valproate- treated mice, combination of lithium chloride and valproate led to a reduction in the MST of mice and an increase in the percent of protection of animals treated with PTZ and an increase in the MST of mice as well as the percent of protection in the ST- treated group of mice. Also, the results revealed that the combined administration of LiCl and VAL into mice subjected to the test convulsive agents resulted in reduced serum and brain concentration of electrolytes in FTZ-treated animals. Also, significant lowering only in the brain Na+, K+ and Cd2+ contents was observed in mice treated with ST

Comparative study of the depressor responses to verapamil hydrochloride following its intravenous, oral and rectal administration

In this study, verapamil hydrochloride [Ver HCL] was formulated in rectal suppository dosage form using different suppository bases. The permeation of the drug through standard cellophane membrane and its dissolution in aqueous medium for different formulations were carried out at 37C. The water-soluble base, polyethylene glycol [PEG], showed the highest release of the drug. The drug release characteristics indicated adherence to first-order kinetics. Using rabbits as experimental animals, in vivo studies of the depressor responses of two different suppository formulations of Ver HCL were compared with those of non-formulated intravenous and oral Ver HCL. It was concluded that rectal administration of Ver HCL brought a more rapid onset and more intense depressor action than those observed following oral ingestion of the same drug. This change was evident with formulation A and might be explained by the rapid dissolution of the water-soluble base in the small amount of fluids presented in the rectum which allows a more rapid release of the drug

Combined anticonvulsant activity of verapamil and phenobarbitone in mice

This study aimed to investigate the anticonvulsant activity of different combinations of phenobarbitone and verapamil. The effect of intraperitoneal[ip] administration of verapamil into mice in a dose of 10 mg/kg on the anticonvulsant activity of phenobarbitone [PB] injected ip in doses of 10, 20, 30 and 40 kg/mg was investigated. Verapamil was allowed to act for five minutes and phenobarbitone for thirty minutes prior to injection of the convulsive agents. Verapamil was given either alone or in combination with different doses of phenobarbitone. Convulsions were induced in animals by pentylenetetrazole [PTZ] in a dose of 100 mg/kg or by strychnine in a dose of 1 mg/kg

Influence of the combined administration of verapamil and phenobarbitone on brain and serum electrolytes in mice

This study was conducted to investigate the mechanism of action of phenobarbitone and verapamil and their concurrent use as anticonvulsant agents against chemically-induced seizures. Brain and serum Na+, Ca2+, K+ ions were measured in different groups of mice; those receiving saline [control] and others receiving the convulsive agent pentylenetetrazole in a dose of 100 mg/kg or strychnine in a dose of 1 mg/kg. In addition, brain and serum electrolytes were measured in mice treated with verapamil in a dose of 10 mg/kg and different doses of phenobarbitone in a doses of 10, 20, 30 and 40 mg/kg] as well as various combination of one dose level of verapamil with the four selected dose levels of phenobarbitone. The results revealed that the ip administration of phenobarbitone in its selected four dose levels was able to significantly and dose-dependently lower the brain calcium level. Moreover, the co-administration of phenobarbitone in its four dose levels with the fixed dose of verapamil [10 mg/kg] was found to bring about lowering of the brain calcium content in all groups of mice treated with the various verapamil- phenobarbitone combinations

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

Relationship between serum levels of theopylline and its clinical effects in patients with obstructive lung diseases

The present study comprised twenty patients [7 females and 13 males] classified into 2 groups; group A involved 10 patients with bronchial asthma. Group B included 10 patients with chronic bronchitis together with emphysema. For all patients, liver function tests including total serum proteins, serum albumin, bilirubin, aspartate transaminase [AST] alanine transaminase [ALT], alkaline phosphatase [ALP] as well as serum creatinine were carried out before the start of treatment with theophylline. This drug was given in a dose of 10 mg/kg body weight. In group A, the mean serum theophylline level was 13.9 +/- 7.0 mug/ml 2 hours following drug administration. Out of the 10 patients, 4 patients were complaining of mild side effects. Moderate toxicity was observed in only 2 patients and was accompanied by serum drug levels above 20 mug/ml. All patients in group A showed clinical improvement which was confirmed by the pulmonary function tests [FER and PEV1]. Concerning B of patients, the mean serum theophylline level 4 hours after administration was 15.7 +/- 5.2 mu g/ml, whereas the mean trough level averaged 13.04 + 4.7 g/ml. All patients in this group displayed symptomatic relief of dyspnea. Out of the 10 patients in group B, only one patient experienced side effects. This patient showed serum theophylline concentration above 20 mu g/ml. In conclusion, for asthmatic patients, the measurement of the theophylline level in blood, when the drug is administered chronically, will guard against the development of toxicity through proper adjustment of the dosage by determination of its serum level. Besides, in patients with irreversible obstructive lung disease, the use of sustained-release preparations is preferred because of the low incidence of toxicity