Fluphenazine-induced acute and tardive dyskinesias in monkeys

Abstract

Five Cebus 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 progressed, 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 The three monkeys that completed 1 year of treatment with fluphenazine were then withdrawn from the drug.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.

Computer-Assisted Video Assessment of Dyskinetic Movements

“…Domino and Kovacic (1983), in fact, concluded that of 121 monkeys that have been given neuroleptics in several published studies, most developed only the acute dystonic or parkinsonism syndrome, and only 10 developed TD (some of those of Gunne and Barany, 1976;Bedard et al, 1977;McKinney et al, 1980). Kovacic and Domino (1984), Johansson (1989), and Gunne et al (1984) subsequently increased this sample, but the number of documented cases is clearly very low.…”

Pargyline reduces/prevents neuroleptic-induced acute dystonia in monkeys

“…These neurological side effects of neuroleptic drugs are troublesome and occasionally dangerous for patients. Similar syndromes are observed in monkeys treated with neuroleptics, including dystonic posturing of the face, trunk, and limbs, buccolinguo-masticatory movements (BLM), and a hyperactive state characterized by purposeless, restless movements resembling akathisia (AKA) (Gunne and Barany 1976;Bedard et al 1977;Meldrum et al 1977;Weiss et al 1977;Casey et al 1980;Liebman and Neale 1980;Porsolt and Jalfre 1981;Kovacic and Domino 1984). These behaviors typically evolve together over 'the course of repeated exposure to neuroleptics and Offprint requests to: D.E.…”

Cebus apella, a nonhuman primate highly susceptible to neuroleptic side effects, carries the GLY9 dopamine receptor D3 associated with tardive dyskinesia in humans

“…[18][19][20] Challenged with a typical antipsychotic, this monkey readily develops syndromes similar to acute dyskinesia in humans. 18,19 Similarly, long-term treatment with neuroleptics leads to a chronic state resembling TD.…”

“…[18][19][20] Challenged with a typical antipsychotic, this monkey readily develops syndromes similar to acute dyskinesia in humans. 18,19 Similarly, long-term treatment with neuroleptics leads to a chronic state resembling TD. [18][19][20] The acute effect of antipsychotics in C. apella previously sensitized to neuroleptics is predictive of the TD potential in humans and is generally assessed prior to initiating clinical trails.…”

“…18,19 Similarly, long-term treatment with neuroleptics leads to a chronic state resembling TD. [18][19][20] The acute effect of antipsychotics in C. apella previously sensitized to neuroleptics is predictive of the TD potential in humans and is generally assessed prior to initiating clinical trails. 21,22 C. apella is at least five times more susceptible to develop EPS than humans.…”