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.