Abstract
FiveCebus apella monkeys were treated with biweekly injections of fluphenazine enanthate (0.1–3.2 mg/kg IM). Three of these completed 1 full year of treatment, one injured its leg after 6 months of treatment and was killed, and another died of unknown causes after 9 months of treatment. All monkeys displayed abnormal movements corresponding to the early appearing extrapyramidal symptoms of neuroleptic-treated patients. These consisted initially of slowing or absence of volitional movement, trembling of the hands, trembling of the entire body, and general drowsy behavior. As treatment progessed, a variety of abnormal postures and movements appeared after each injection that were not exacerbated by drug withdrawal and, as tested at the end of the year, could be abolished or prevented with benztropine mesylate (0.2–0.5 mg/kg IM). The three monkeys that completed 1 year of treatment with fluphenazine were then withdrawn from the drug. After withdrawal, all three developed movements similar in appearance to those of patients with tardive dyskinesia (TD). Reinstitution of fluphenazine treatment, as tested in one monkey, abolished all movements resembling TD.
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Baldessarini RJ, Cole JO, Davis JM, Gardos G, Preskorn SH, Simpson GM, Tarsy D (1980) Tardive dyskinesia: A task force report of the American Psychiatric Association. American Psychiatric Association, Washington DC
Bárány S, Ingvast A, Gunne LM (1979) Development of acute dystonia and tardive dyskinesia in Cebus monkeys. Res Commun Chem Pathol Pharmacol 25:269–279
Bedard P, Delean J, LaFleur J, LaRochelle L (1977) Haloperidol-induced dyskinesias in the monkey. J Can Sci 4:197–201
Casey DE, Gerlach J, Christensson E (1980) Dopamine, acetylcholine and GABA effects in acute dystonia in primates. Psychopharmacology 70:83–87
Csernansky JG, Grabowski K, Cervantes J, Kaplan J, Yesavage JA (1981) Fluphenazine decanoate and tardive dyskinesia: A possible association. Am J Psychiatry 138:1363–1365
Deneau, GA, Crane GE (1969) Dyskinesia in rhesus monkeys tested with high doses of chlorpromazine. In: Crane GE, Gardner R (eds) Psychotropic drugs and dysfunction of the basal ganglia. US Public Health Service, Washington DC, pp 12–14
Deuel RK (1969) Neurological examination of rhesus monkeys treated with high doses of chlorpromazine. In: Crane GE, Gardner R (eds) Psychotropic drugs and dysfunction of the basal ganglia. US Public Health Service, Washington DC, pp 15–18
Ezrin-Waters, C, Seeman MV, Seeman P (1981) Tardive dyskinesia in schizophrenic outpatients: Prevalence and significant variables. J Clin Psychiatry 42:16–22
Gibson A (1978) Depot injections and tardive dyskinesia. Br J Psychiatry 132:361–365
Gunne LM, Bárány S (1976) Haloperidol-induced tardive dyskinesia in monkeys. Psychopharmacology 50:237–240
Hăggstròm JE, Anderson U, Gunne LM (1981) A primate model for tardive dyskinesia: Postmortem biochemical findings. In: Perris C, Sruwe G, Jansson B (eds) Biological psychiatry. Elsevier North Holland, Amsterdam, pp 837–839
Johnson DAW (1973) The side effects of fluphenazine decanoate. Br J Psychiatry 123:519–522
Johnson DAW, Freeman HL (1973) Drug defaulting by patients on long-acting phenothiazines. Psychiatr Med 3:115–119
Kovacic B, Domino EF (1982) A monkey model of tardive dyskinesia (TD): Evidence that reversible TD may turn into irreversible TD. J Clin Psychopharmacology 2:305–307
Liebman J, Neale R (1980) Neuroleptic-induced acute dyskinesias in squirrel monkeys: Correlation with propensity to cause extrapyramidal side effects. Psychopharmacology 68:25–29
McKinney WT, Moran EC, Kraemer GW, Prange AJ Jr (1980) Long-term chlorpromazine in rhesus monkeys: Production of dyskinesias and changes in social behavior. Psychopharmacology 72:35–39
Paulson GW (1972) Dyskinesias in rhesus monkeys. Trans Am Neurol Assoc 97:109–110
Paulson GW (1973) Dyskinesias in monkeys. Adv Neurol 1:647–650
Sande MA, Mandell GE (1980) Antimicrobial agents: Miscellaneous antibacterial agents: antifungal and antiviral agents. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 1222–1248
Smith RC, Strizich M, Klass D (1978) Drug history and tardive dyskinesia. Am J Psychiatry 135:1402–1403
Waddington JL (1982) Tardive dyskinesia, fluphenazine decanoate, and haloperidol. Am J Psychiatr 139:703–704
Weiss B, Santelli S, Lusink G (1977) Movement disorders induced in monkeys by chronic haloperidol treatment. Psychopharmacology 53:289–293
Weiss B, Santelli S (1978) Dyskinesias evoked in monkeys by weekly administration of haloperidol. Science 200:799–801
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Kovacic, B., Domino, E.F. Fluphenazine-induced acute and tardive dyskinesias in monkeys. Psychopharmacology 84, 310–314 (1984). https://doi.org/10.1007/BF00555204
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DOI: https://doi.org/10.1007/BF00555204