RT Journal Article SR Electronic T1 BINDING OF CYPROHEPTADINE-(N-METHYL-14C) BY HUMAN BLOOD PLATELETS: INHIBITION BY PHENOTHIAZINES AND TRICYCLIC ANTIDEPRESSANTS JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 171 OP 176 VO 185 IS 1 A1 GAUT, z. N. YR 1973 UL http://jpet.aspetjournals.org/content/185/1/171.abstract AB Cyproheptadine, an antihistaminic antiserotonergic agent, inhibits platelet aggregation. This study describes the accumulation, in vitro, of 14C-cyproheptadine by the human platelet and inhibition thereof by phenothiazines and tricyclic antidepressants. Platelets were incubated at 37°C for various times in Ca++- and Mg++-free Krebs-Ringer-bicarbonate buffer under O2-CO2 (95:5, v/v). When incubated for two minutes with 14C-cyproheptadline, 0.5 mM to 1.4 µM, platelets accumulated radioactivity with gradients ([I]/ [O]) of 65 to 290, respectively. At all concentrations of the drug, no additional uptake occurred upon increasing incubations to 60 minutes. Under all circumstances, > 98% of platelet-associated radioactivity migrated with anthentic cyproheptadine on thin layers of silicic acid. At an initial concentration of 0.014 mM 14C-cyproheptadine and with 10 minute incubations, 50% suppression of the radioactivity gradient occurred with chlorpromazine (0.13 mM), phenotimiazine (0.13 mM), promethazine (0.15 mM), amtriptyline (0.23 mM), desipramine (0.20 mM), imipramine (0.16 mM), nortriptyline (0.10 mM) and protriptyline (0.13 mM). Several other basic compounds, including histamine and serotonin, and metabolic inhibitors were not inhibitory. The lack of effect by incubation in the cold or by metabolic inhibitors, the rapidity of uptake of 14C-cyproheptadine and the localization of most of the radioactivity in the 120,000 x g fraction from platelet homogenate indicate that accumulation is mainly due to binding of cyproheptadine to the platelet membrane rather timan active transport. Binding of the drug to platelets incubated in plasma Suggests this phenomenon may also occur in vivo. 14C-cyproheptadine is not metabolized by the platelet. The possible relationship between the binding of cyproheptadine to the platelet and inhibition of aggregation is discussed. © 1973 by The Williams & Wilkins Company