INHIBITION OF NEURONAL DOPAMINE UPTAKE BY SOME ANTIALLERGIC DRUGS

The effects of 10 antiallergic drugs (astemizole, azelastine, ebastine , emedastine, epinastine, ketotifen, oxatomide, terfenadine, pemirolas t and tranilast) on neuronal dopamine uptake were examined. Some drugs examined showed a concentration-dependent inhibition of [H-3]dopamine uptake into synaptosomal preparations of the rat striatum. The inhibi tion constant (K-i) values were 231-876 nM for ebastine, terfenadine, oxatomide and astemizole. The specific binding of [H-3] phenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine) (GBR12935) to the rat striatal me mbranes was also inhibited by these antiallergic drugs. There was a go od correlation between the degrees of inhibition of [H-3]dopamine upta ke and [H-3]GBR12935 binding. Then, the behavioral excitement induced by L-DOPA (100 mg/kg, s.c.) plus pargyline hydrochloride (80 mg/kg, i. p.) in mice was significantly enhanced by i.p. treatment with ebastine (10 mg/kg) and astemizole (5 mg/kg). These results suggest that the n euronal dopamine uptake is inhibited by some antiallergic drugs, espec ially ebastine. (C) 1998 Elsevier Science B.V. All rights reserved.