The effect of tetrahydroisoxazolopyridinol (THIP) in tardive dyskinesia: a new gamma-aminobutyric acid agonist.

Abstract

gamma-Aminobutyric acid (GABA) agonists have been proposed for the treatment of tardive dyskinesia, but their therapeutic potential has been limited by side effects and toxicity. To elucidate further the role of GABA in neuroleptic-induced dyskinesias, we evaluated tetrahydroisoxazolopyridinol (THIP), a new, less toxic GABA analog and GABA receptor agonist, in both a dose-finding (single-dose) pilot study with five patients and a longer (four-week) placebo-controlled study with 13 patients. The patients were videotaped during a standardized examination; tardive dyskinesia, parkinsonian symptoms, and eye-blinking rates were rated blindly and randomly. The maximal short-term dose of THIP was 10 to 25 mg, whereas in the longer-term study the highest daily dose ranged from 20 to 120 mg. Tardive dyskinesia was unchanged during THIP treatment, but preexisting parkinsonism increased significantly and eye-blinking rates decreased. Psychiatric symptoms showed no significant changes, although tension and depression lessened. Side effects included sedation, confusion, dizziness, vomiting, and myoclonic jerks. Although THIP is not an effective new treatment for tardive dyskinesia, more specific GABA agonists should be evaluated in future studies of this syndrome.

• Authors: S Korsgaard, D E Casey, J Gerlach, O Hetmar, B Kaldan, L B Mikkelsen
• Journal: Archives of general psychiatry (Arch Gen Psychiatry) Vol. 39 Issue 9 Pg. 1017-21 (Sep 1982) ISSN: 0003-990X [Print] United States
• PMID: 6126170 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Antipsychotic Agents
• Isoxazoles
• Oxazoles
• Placebos
• gaboxadol

Topics

• Adult
• Aged
• Analgesics (administration & dosage, adverse effects, therapeutic use)
• Antipsychotic Agents (adverse effects)
• Blinking (drug effects)
• Clinical Trials as Topic
• Confusion (chemically induced)
• Dizziness (chemically induced)
• Dyskinesia, Drug-Induced (drug therapy)
• Female
• Humans
• Isoxazoles (administration & dosage, adverse effects, therapeutic use)
• Male
• Mental Disorders (drug therapy)
• Middle Aged
• Oxazoles (therapeutic use)
• Parkinson Disease, Secondary (drug therapy)
• Placebos
• Vomiting (chemically induced)