Effects of psychotropic agents on the physical properties of platelet membranes in vitro.
Normal platelet membranes were exposed in vitro to a variety of psychotropic medications commonly used in the treatment of patients with psychiatric disorders. Changes in structural order at the hydrocarbon region of the drug-exposed membranes were determined by steady-state fluorescence polarization measurements employing the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Chlorpromazine, an aliphatic phenothiazine, produced a significant increase in DPH fluorescence polarization at concentrations from 2-200 microM. Thioridazine, a piperidine phenothiazine, and three piperazine derivatives, perphenazine, trifluoperazine, and fluphenazine, produced significant increases in this parameter at concentrations from 20-200 microM. The other agents tested, including thiothixene, lithium, antidepressants, anxiolytics, and anticonvulsants, were without effect in the concentration ranges examined. The phenothiazine-induced increase in DPH fluorescence polarization apparently depended on the structure of the phenothiazine nucleus; changes in side-chain structure appeared to modulate this effect, most likely by altering the inherent membrane solubility of the agents.
Zubenko
G S
GS
Cohen
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BM
D014150:Antipsychotic Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D004161:Diphenylhexatriene; D005454:Fluorescence Polarization; D006801:Humans; D066298:In Vitro Techniques; D010640:Phenothiazines; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010640:Phenothiazines; D011619:Psychotropic Drugs; D004161:Diphenylhexatriene