Thenalidine

ABSTRACT. Hospital records of 256 patients discharged with a diagnosis of agranulocytosis during 1973–78 in the Stockholm County region were reviewed. In 84 cases the neutropenia was probably caused by drugs other than cytostatics, giving an annual incidence of 0.009%c. The commonest drugs were sulfonamides, thyreostatics and thenalidine. Metamizole (Dipyrone), previously the commonest cause of drug‐induced neutropenia in Sweden, has not been marketed since 1973 and, as a result, only two cases were seen (the drug had been obtained abroad). Comparison of the number of cases of neutropenia with drug sales showed the highest frequency for thenalidine, followed by thyreostatics, penicillamine and sulfonamides, in that order. Only about 35% of the cases had been reported to the authorities. Nine (11%) of the patients died. It is concluded that the pattern of drugs causing neutropenia has changed in Sweden since the studies from the latter half of the 60s and that early detection of this side‐effect requires directed and continuous follow‐up studies.

Antihistaminic drugs of various chemical structure (chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, thenalidine) were tested on their action on the central serotonin system in mice. The test used was the antagonism to behavioral syndrome produced by D, L-5-hydroxytryptophan (5-HTP). Clemastine, promethazine and thenalidine inhibited 5-HTP-induced syndrome in doses of much lower than those inhibiting locomotor activity. Similar but weaker effect was produced by chlorcyclizine and diphenhydramine. It could be suggested that these compounds exert central antiserotonergic action. Chloropyramine and, more strongly, chlorpheniramine potentiated the action of 5-HTP; this may be due to the inhibition of serotonin uptake. Only mepyramine in these tests did not show any action on the central serotonin system.