Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal

This study was aimed at examining the effects of two frequently used Ca2+ antagonists, nitrendipine and verapamil, on withdrawal after cessation of long-term treatment with the anticonvulsant drug carbamazepine in rats. The 48-h interruption of long-term (21 days) carbamazepine treatment led to the appearance of withdrawal characterized by increases in seizure intensity, the percentage of rats with tonic seizures and mortality. Oral treatment with the two calcium antagonists in combination with carbamazepine abolished the signs of carbamazepine withdrawal. Seizure intensity, the percentage of rats with tonic seizures and mortality in the groups treated with the combinations of carbamazepine + verapamil and carbamazepine + nitrendipine were significantly lower than those of the group of rats treated with carbamazepine alone. In conclusion, some Ca2+ antagonists could attenuate the manifestations of anticonvulsant withdrawal and thus could be used as adjuvants in long-term anticonvulsant therapy.