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Research Article| Volume 30, ISSUE 3, P225-232, August 01, 1991

Dopamine blocking activity of clomipramine in patients with obsessive-compulsive disorder

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      Abstract

      While many data suggest that Obsessive-Compulsive Disorder (OCD) is an illness accompanied by dysregulation of the serotonergic system, interesting clinical evidence and animal studies also suggest possible dysregulation of the dopaminergic (DA) system. In order to determine whether clomipramine (CMI), an antiobsessional agent, is capable of altering DA function, we performed a neuroleptic radioreceptor assay (NRRA) on plasma samples from OCD patients before and after treatment in a double-blind, placebo controlled trial of CMI. CMI produced mild but significant DA D-2 receptor binding activity in an in vitro assay. The degree of dopamine binding activity did not correlate with clinical response to clomipramine. Because it has been suggested that another drug with antiobsessional efficacy, fluoxetine, may also have dopamine blocking properties, it may be speculated that antidopaminergic activity in combination with serotonergic effects is involved in antiobsessional activity of effective agents for some patients.
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      References

        • Baxter L.R.
        • Swartz J.M.
        • Mazziotta J.C.
        • et al.
        Cerebral glucose metabolic rates in non-depressed patients with obsessive-compulsive disorder.
        Am J Psychiatry. 1988; 145: 1560-1563
        • Benkelfat C.
        • Murphy D.L.
        • Zohar J.
        • Hill J.L.
        • Grover G.
        • Insel T.R.
        Clomipramine in obsessive-compulsive disorder.
        Arch Gen Psychiatry. 1989; 46: 23-44
        • Carlsson A.
        • Lindquist M.
        Effect of chlorpromazine or haloperidol on formation of 3-methoxy tyramine and normetanephrine in mouse brain.
        Acta Pharmacol Toxicol. 1963; 20: 140-144
        • CIBA Pharmaceutical Co.
        Anafranil package insert.
        1990 (Summit, NJ)
        • Cohen B.M.
        • Herschel M.
        • Aoba A.
        Neuroleptic, antimuscarinic, and antiadrenergic activity of chlorpromazine, thioridazine, and their metabolites.
        Psychiatry Res. 1979; 1: 199-208
        • Cohen B.M.
        • Lipinski P.Q.
        • Harris
        • Pope H.G.
        • Friedman M.
        Clinical use of the radioreceptor assay for neuroleptics.
        Psychiatry Res. 1980; 2: 173-178
        • Creese I.
        • Snyder S.H.
        A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood.
        Nature. 1977; 270: 180-182
        • Delini-Stula A.
        • Vassout A.
        Modulation of dopamine-mediated behavioural responses by antidepressants: Effects of single and repeated treatment.
        Eur J Pharmacol. 1976; 58: 443-451
        • DeVeaugh-Geiss J.
        • Landau P.
        • Katz R.
        Preliminary results from a multicenter trial of clomipramine in obsessive compulsive disorder.
        Psychopharmacol Bull. 1989; 25: 36-40
        • Eilinwood E.H.
        Amphetamine psychosis I. Description of the individual and the process.
        J Nerv Ment Dis. 1967; 144: 273-283
        • Engelhardt D.M.
        • Rosen B.
        • Freedman N.
        • Margolis R.
        Phenothiazine in prevention of psychiatric hospitalization.
        Arch Gen Psychiatry. 1967; 16: 98-101
        • Goodman W.K.
        • Rasmussen S.A.
        • Price L.H.
        • Mazure C.
        • Heninger G.R.
        • Charney D.S.
        Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.
        Arch Gen Psychiatry. 1989; 46: 1006-1011
        • Goodman W.K.
        • Price L.P.
        • Anderson G.M.
        Drug response and obsessive compulsive disorder subtypes.
        in: Presented at the 142nd annual meeting of the American Psychiatric Association, San Francisco1989
        • Grimshaw I.
        Obsessional disorder and neurological illness.
        J Neurol Neurosurg Psychiatry. 1964; 27: 229
        • Halaris A.E.
        • Freedman D.X.
        Psychotropic drugs and dopamine uptake inhibition.
        in: Freedman D. Biology and the Major Psychoses. Raven Press, New York1975
        • Hall H.
        • Ögren S.E.
        Effects of antidepressants on different receptors in the brain.
        Eur J Pharmacol. 1981; 70: 393-407
        • Insel T.R.
        • Hamilton J.A.
        • Guttmacher L.B.
        • Murphy D.L.
        D-amphetamine in obsessive-compulsive disorder.
        Psychopharmacology. 1983; 80: 231-235
        • Insel T.R.
        • Mueller E.A.
        • Alterman I.
        • Linnoila M.
        • Murphy D.L.
        Obsessive-compulsive disorder and serotonin: is there a connection?.
        Biol Psychiatry. 1985; 20: 1174-1188
        • Jenike M.A.
        • Baer L.
        • Summergrad P.
        • Weilburg J.B.
        • Holland A.
        • Seymour R.
        Obsessive-compulsive disorder: A double-blind, placebo-controlled trial of clomipramine in 27 patients.
        Am J Psychiatry. 1989; 146: 1328-1330
        • Jenike M.A.
        • Buttolph L.
        • Baer L.
        • Ricciardi J.
        • Holland A.
        Open trial of fluoxetine in obsessive-compulsive disorder.
        Am J Psychiatry. 1989; 146: 909-911
        • Leonard H.L.
        • Swedo S.E.
        • Rapoport J.L.
        • et al.
        Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison.
        Arch Gen Psychiatry. 1989; 46: 1088-1092
        • Lipinski J.F.
        • Mallya G.
        • Zimmerman P.
        • Pope H.G.
        Fluoxetine-induced akathisia: Clinical and theoretical implications.
        J Clin Psychiatry. 1989; 50: 339-342
        • Mavissakalian M.
        • Turner S.M.
        • Michelson L.
        • Jacob R.
        Tricyclic antidepressants in obsessive-compulsive disorder: Anti-obsessional or antidepressant agents? II.
        Am J Psychiatry. 1985; 142: 572-576
        • Meltzer H.Y.
        • Young M.
        • Metz J.
        • Fang V.S.
        • Schyve P.M.
        • Arora R.C.
        Extrapyramidal side effects and increased serum prolactin following fluoxetine, a new antidepressant.
        J Neurol Transm. 1979; 45: 165-175
        • Nee L.E.
        • Caine E.D.
        • Polinsky R.J.
        • Eldridge R.
        • Ebert M.H.
        Gilles de la Tourette's syndrome: Clinical and family study of 50 cases.
        Ann Neurol. 1980; 7: 41-49
        • Peroutka S.J.
        • Snyder S.H.
        Relationship of neuroleptic drug effects at brain dopamine, x-adrenergic, and histamine receptors to clinical potency.
        Am J Psychiatry. 1980; 137: 1518-1522
        • Persson S.A.
        Psychopharmacology. 1979; 66: 13-17
        • Randrup A.
        • Braestrup C.
        Uptake inhibition of biogenic amines by newer antidepressant drugs: Relevance to the dopamine hypothesis of depression.
        Psychopharmacology. 1977; 53: 309-314
        • Sunderland T.
        • Cohen B.M.
        Blood to brain distribution of neuroleptics.
        Psychiatry Res. 1987; 20: 299-305
        • Swedo S.E.
        • Rapoport J.L.
        • Cheslow D.L.
        • et al.
        High prevalence of obsessive compulsive symptoms in patients with Sydenham's chorea.
        Am J Psychiatry. 1989; 146: 246-249
        • Thoren P.
        • Asberg M.
        • Bertilsson L.
        • Mellström B.
        • Sjökvist F.
        • Träskman L.
        Clomipramine treatment of obsessive-compulsive disorder: A controlled clinical trial.
        Arch Gen Psychiatry. 1980; 37: 1289-1294
        • Waldmeier P.C.
        Effects of antidepressant drugs on dopamine uptake and metabolism.
        J Pharm Pharmacol. 1982; 24: 391-394
        • White K.
        • Keck P.E.
        • Lipinski J.
        Serotonin-uptake inhibitors in obsessive-compulsive disorder: a case report.
        Comps Psychiatry. 1986; 27: 211-214
        • Zohar J.
        • Insel T.R.
        Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology.
        Biol Psychiatry. 1987; 22: 667-687
        • Zohar J.
        • Insel T.R.
        • Zohar-Kudovich R.C.
        • Hill J.L.
        • Murphy D.L.
        Serotonergic responsivity in obsessive compulsive disorder.
        Arch Gen Psychiatry. 1988; 45: 167-172