Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties.

Diphenylpyraline hydrochloride (DPP) is used clinically as an antihistamine drug, but its neurobiological effects are not completely understood. Voltammetry and microdialysis were used to investigate potential actions of DPP on the dopamine system. Voltammetric monitoring of dopamine signals in mouse nucleus accumbens slices showed that DPP (10 microM) markedly inhibited dopamine uptake. There was a 20-fold increase in apparent Km for dopamine uptake, while Vmax was unchanged. Microdialysis experiments demonstrated that DPP (5 mg/kg, i.p.) elevated extracellular dopamine levels (approximately 200%) in mouse nucleus accumbens. DPP (5 and 10 mg/kg) also induced locomotor activation. All of the effects of DPP were comparable with those of cocaine. Taken together, these results indicate that DPP acts as a competitive dopamine transporter inhibitor similar to cocaine.