Research Article| Volume 20, ISSUE 8, P866-873, August 1985

Different effects of centrally acting drugs on rabbit platelet aggregation: With special reference to selective inhibitory effects of antipsychotics and antidepressants

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      Twenty-four drugs, consisting of antipsychotics, tricyclic antidepressants, other centrally acting drugs, and related compounds, were studied for their effects on aggregation of rabbit platelets.
      • 1.
        1. Phenothiazine neuroleptics, haloperidol, sultopride, tricyclic antidepressants, sulpiride, atropine, and propranolol showed a selective inhibitory effect on the collagen-induced aggregation, but not on aggregations induced by arachidonic acid (AA) or adenosine diphosphate (ADP). These drugs are thought to inhibit the liberation of AA from phospholipids in platelet membranes, suggesting that they might inhibit phospholipases.
      • 2.
        2. Mepyramine, promethazine, phentolamine, and clozapine inhibited the aggregations evoked by collagen and AA, but failed to inhibit the ADP-induced aggregation. These drugs might inhibit the generation of prostaglandin endoperoxides or thromboxanes.
      • 3.
        3. Phenobarbital, phenytoin, procaine, lidocaine, flurazepam, trihexyphenydil, and lithium carbonate did not inhibit any kind of aggregation at the concentrations used.
      The clinical and pharmacological significance of these findings is discussed; it seems that the inhibitory effects of antipsychotics and antidepressants on platelet aggregation are closely related to the specific clinical and psychotropic effects of these drugs, but not to other actions.
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        • Burki H.R.
        • Eisenberger E.
        • Sayers A.C.
        • White T.G.
        Clozapine and the dopamine hypothesis of schizophrenia: A critical appraisal.
        Pharmacopsychiatria. 1975; 8: 115
        • Boullin D.J.
        • Grahame-Smith D.G.
        • Grimes R.P.J.
        • Woods H.F.
        Inhibition of 5-hydroxytryptamine-induced human blood platelet aggregation by chlorpromazine and its metabolites.
        Br J Pharmacol. 1975; 53: 121
        • Boullin D.J.
        • Green A.R.
        • Grimes R.P.J.
        Human blood platelet aggregation induced by dopamine, 5-hydroxytryptamine and analogues.
        J Physiol (Lond). 1975; 252: 46
        • Boullin D.J.
        • Grimes R.P.J.
        • Orr M.W.
        The actions of flupenthixol upon 5-hydroxytryptamine and dopamine by human blood platelets.
        Br J Pharmacol. 1975; 55: 555
        • Clement-Cormier Y.C.
        • Kebabian J.W.
        • Petzold G.L.
        • Greengard P.
        Dopamine-sensitive adenylate cyclase in mammalian brain: A possible site of action of antipsychotic drugs.
        in: Proc Natl Acad Sci USA. 71. 1974: 1113
        • Creese I.
        • Burt D.R.
        • Snyder S.H.
        Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs.
        Science. 1976; 192: 481
        • Davis J.M.
        Dose equivalence of the antipsychotic drugs.
        J Psychiatr Res. 1974; 11: 65
        • Ishigooka J.
        • Tanaka K.
        • Suzuki Y.
        • Katori M.
        • Miura S.
        Selective inhibitory effects of chlorpromazine and imipramine on platelet aggregation.
        Int Pharmacopsychiatry. 1980; 15: 270
        • Jenner P.
        • Clow A.
        • Reavill C.
        • Theodorou A.
        • Marsden C.D.
        Stereoselective actions of substituted benzamide drugs on central dopamine mechanisms.
        J Pharm Pharmacol. 1980; 32: 39
        • Kayama N.
        • Sakaguchi K.
        • Kaneko S.
        • Kubota T.
        • Fukuzawa T.
        • Kawamura S.
        • Yoshimoto T.
        • Yamamoto S.
        Inhibition of platelet aggregation by l-alkylimidazole derivatives, thromboxane A synthetase inhibitors.
        Prostaglandins. 1981; 21: 543
        • Keller H.H.
        • Bartholini G.
        • Pletcher A.
        Increase of 3-methoxy-4-hydroxyphenylethylene glycol in rat brain by neuroleptic drugs.
        Eur J Pharmacol. 1973; 23: 183
        • Kunze H.
        • Bohn E.
        • Vogt W.
        Effects of local anaesthetics on prostaglandin biosynthesis in vitro.
        Biochim Biophys Acta. 1974; 360: 260
        • Kunze H.
        • Nahas N.
        • Traynor J.R.
        • Wurl M.
        Effects of local anaesthetics on phospholipases.
        Biochim Biophys Acta. 1976; 441: 93
        • Mills D.C.B.
        • Roberts G.C.K.
        Membrane active drugs and the aggregation of human platelets.
        Nature (Lond). 1967; 213: 35
        • Nagayama H.
        • Hingtgen J.N.
        • Aprison M.H.
        Pre- and postsynaptic serotonergic manipulations in an animal model of depression.
        Pharmacol Biochem Behav. 1980; 13: 575
        • Nagayama H.
        • Hingtgen J.N.
        • Aprison M.H.
        Postsynaptic action by four antidepressant drugs in an animal model of depression.
        Pharmacol Biochem Behav. 1981; 15: 125
        • Rysanek R.
        • Svehla C.
        • Spankova H.
        • Mlejnkova M.
        The effect of tricyclic antidepressive drugs on adrenaline and adenosine diphosphate induced aggregation.
        J Pharm Pharmacol. 1966; 18: 616
        • Snyder S.H.
        • Greenberg D.
        • Yamamura H.I.
        Antischizophrenic drugs: Affinity for muscarinic cholinergic receptor sites in the brain predicts extrapyramidal effects.
        J Psychiatr Res. 1974; 11: 91
        • Stawarts R.J.
        • HIll H.
        • Robinson P.
        • Setler J.V.
        • Sulser F.
        On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain.
        Psychopharmacologia. 1975; 43: 125
        • Takai Y.
        • Kishimoto A.
        • Kawahara A.
        • Minakuchi R.
        • Sano K.
        • Kikkawa U.
        • Mori T.
        • Yu B.
        • Kaibuchi K.
        • Nishizuka Y.
        Calcium and phosphatidylinositol turnover as signaling for transmembrane control of protein phosphorylation.
        Adv Cyclic Nucleotide Res. 1981; 14: 301
        • Tanaka K.
        • Harada Y.
        • Iwata M.
        • Katori M.
        Potentiation of anti-aggregating activity of PGI2 by 7-ethoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1(2H)-phthalazinone (EG-626) in rabbit platelets in vitro.
        Prostaglandins. 1980; 20: 225
        • Tanaka K.
        • Matoba A.
        • Harada Y.
        • Katori M.
        Reappearance of anti-aggregating activity of thromboxane synthatase inhibitors in the presence of aortic rings.
        in: 8th International Congress of Pharmacology. 1981 (Abstract 741)
        • Vanderhoek J.Y.
        • Feinstein M.B.
        Local anesthetics, chlorpromazine and propranolol inhibit stimulus-activation of phospholipase A2 in human platelets.
        Mol Pharmacol. 1979; 16: 171
        • Vermylen J.
        Physiology of haemostasis.
        in: de Gaetano G. Garattini S. Platelets: A Multidisciplinary Approach. Raven, New York1978: 3
        • Worms P.
        Behavioral pharmacology of the benzamides as compared to standard neuroleptics.
        Adv Biochem Psychopharmacol. 1982; 35: 7