The effects of prodipine and budipine on 14C-5-hydroxytryptamine uptake and release by human blood platelets.

The in vitro uptake and release of 14C-5-hydroxy-tryptamine (14C-5-HT) by human blood platelets was examined, which were used in this study as a simple model for serotonergic nerve endings. Experimental conditions allowed measurement of initial velocity of uptake and excluded possible (re)uptake of recently liberated 14C-5-HT in the release studies. The effects of two new antiparkinson drugs, 1-isopropyl-4,4-diphenylpiperdine (prodipine) and its 1-tert-butyl analogue (budipine), on the two opposite transport processes of serotonin were investigated. Prodipine and budipine inhibit the uptake of 14C-5-HT by human blood platelets in a dose-dependent manner. Inhibition of uptake by both drugs is non-competitive; Ki values are 1.1X10(-4) mol/l for prodipine and 9X10(-5) mol/l for budipine, with prodipine additionally showing an effect on Km of serotonin for uptake system. Both substances liberate recently accumulated 14C-5-HT from the platelets. Stimulation of this process is dose-dependent, budipine proving more active than prodipine, both drugs being 5.4 and 4.1 times stronger than amantadine. The observed effects of prodipine and budipine on uptake and release of 14C-5-HT by isolated blood platelets are discussed in the light of other pharmacological activities and the antiparkinson efficacy of these drugs.