Comparative evaluation of anticonvulsant activity of calcium channel blockers in experimental animals.

Pentylenetetrazole (PTZ)-induced convulsions and the maximal electroshock (MES) seizure test were employed to study the anticonvulsant effects of nifedipine (2, 3.5 and 5 mg kg-1), flunarizine (10, 20 and 40 mg kg-1) and diltiazem (10, 15 and 30 mg kg-1). Nifedipine and flunarizine prolonged the latent period and reduced the mean duration of PTZ induced seizures. They also reduced the severity of convulsions and the number of deaths due to PTZ significantly. Nifedipine was more potent in this regard (P < 0.01). All these drugs prolonged the latent period and reduced the duration of tonic extensor phase of MES seizures in a significant manner. Flunarizine was most potent in this test. Complete protection from tonic extensor phase was observed in 10-50% animals pretreated with nifedipine and flunarizine in a dose dependent manner. The response of diltiazem was weak in both these tests. It is concluded that all three calcium channel blockers possess an important but different anticonvulsant effect and their significant clinical use can be made while keeping in view the characteristics of their pharmacological action.

Effect of nifedipine, a calcium channel inhibitor, on sedation produced by reserpine, clonidine and propranolol in mice.

Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.

Effect of calcium salts & related substances on the motility & viability of ejaculated human spermatozoa in vitro.

Effect of four calcium salts, three calcium antagonists, calcium ionophore (A 23187) and calmodulin was studied in vitro on the motility and viability of ejaculated normal human spermatozoa at different time intervals. Effect of calcium salts was also studied on the oligoasthenospermic samples with an original motility of 10 to 30 per cent. Calcium salts were found to improve the sperm motility by 6 to 16 per cent and this may be due to a direct excitatory influence and a protective action of calcium on the spermatozoa since the viability was also improved by 4 to 11 per cent in these cases. A similar improvement in motility (8 to 11%) and viability (5 to 9%) was observed in hypokinetic samples also, Calcium antagonists inhibited the sperm motility and viability significantly. Diltiazem was the most potent drug in this respect, the reduction in motility being by 11 to 22 per cent and in viability by 6 to 14 per cent, after 30 sec of incubation. Calcium ionophore and calmodulin were found to be more potent than calcium antagonists to produce a dose-dependent decrease in sperm motility and viability. The results confirm that ionized calcium plays an important role in the regulation of sperm motility. Although intracellular concentration of calcium may be a better determinant physiologically, the manipulation of extracellular levels in a critical range may promote the sperm motility, viability and other vital functions. This has a potential use in situations like artificial insemination, in vitro fertilization and semen banking. Calcium ionophores and calmodulin need further investigation for a possible use as vaginal spermicides.

A study of some pharmacological actions of carbamazepine and sodium valproate.

Carbamazepine (CA) and sodium valproate (SV) were studied for their actions of central nervous system and neuromuscular junction. CA and SV given ip neither possessed analgesic nor hypothermic activity in rats, nor did they alter the pentobarbitone sleeping time in mice. The drug had no effect on the frog rectus muscle nor did they alter its responses to acetylcholine. Both CA and SV produced a dose related decrease in indirectly evoked contractions of rat diaphragm and cat gastrocnemius muscle without much altering the directly evoked responses. This effect may be due to their local anaesthetic property, which was observed in infiltration test in guinea pigs.

Effect of some drugs on human appendix in vitro.

Muscarinic action of acetylcholine was demonstrated in the human isolated appendix. Histamine-induced contractions seemed to the mediated by H1 receptors. Nicotine and DMPP-induced contractions were mediated through their action on ganglion cells. Experiments with adrenergic drugs suggested the presence of beta receptors.