d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Dyskinesia--Drug-Induced

Eight psychiatric patients with tardive dyskinesia (TD) were treated with single doses of the synthetic met-enkephalin analogue FK 33-824 (1, 2, and 3 mg IM) morphine (10 mg SC) and naloxone, an opiate receptor antagonist (0.8 mg IM). The drug effects were assessed by blind evaluation of randomly sequenced videotapes made before and during treatment. FK 33-824 (1, 2, and 3 mg IM) slightly reduced TD (P < 0.05) and increased preexisting bradykinesia. The effect on TD, however, was pronounced only in patients concurrently treated with neuroleptics in relatively high doses. Morphine had a similar although weaker antihyperkinetic effect, whereas naloxone had no effect. Side effects of FK 33-824 included dizziness, heaviness in the extremities, slurred speech, and dryness of mouth. Morphine caused drowsiness, dizziness, ataxia, and nausea, and naloxone had no side effects. The results do not point to a primary role of enkephalin in the pathophysiology of TD, but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs.

Topics: Aged; Clinical Trials as Topic; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Double-Blind Method; Dyskinesia, Drug-Induced; Endorphins; Enkephalins; Female; Humans; Male; Middle Aged; Morphine; Naloxone; Parkinson Disease, Secondary

We review the results of more than 120 studies of the treatment of tardive dyskinesia with noncatecholaminergic agents. The disorder is thought to arise from dopamine receptor supersensitivity brought on by long term neuroleptic-induced receptor blockade. Ironically, neuroleptics are the most consistently effective treatment of tardive dyskinesia. Nevertheless, it would be desirable to treat it with other compounds. The most intensively studied drugs are the cholinergics, including physostigmine, deanol, choline, and lecithin, but their efficacy has been equivocal. Anticholinergics, opiates, and tryptophan appear to worsen the syndrome or have no effect. Trials of gamma-aminobutyric acid agonists, lithium, and amantadine also produced mixed results. Effectiveness has been claimed for benzodiazepines, estrogens, and pyridoxine,, but the evidence is scant. A small number of preliminary reports on other treatments are also summarized. We discuss briefly the implications of these studies, but methodological problems limit interpretation.

Topics: Amantadine; Anti-Anxiety Agents; Benzodiazepines; Cyproheptadine; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Double-Blind Method; Dyskinesia, Drug-Induced; Enkephalin, Methionine; gamma-Aminobutyric Acid; Humans; Lithium; Parasympathomimetics; Phenytoin; Receptors, Cell Surface; Receptors, Cholinergic; Receptors, GABA-A; Substance Withdrawal Syndrome; Tryptophan