STEREOTYPED BEHAVIOR AND THIORIDAZINE PHARMACODYNAMICS

Project: Research project

Description

A major clinical problem in mentallly retarded children and adults is
stereotyped behavior. Stereotyped behavior includes repetitive invariant
topographic mannerisms, such as body rocking, head weaving, etc.
Thioridazine (Mellaril ) is a phenothiazine antipsychotic drug that is the
most frequently used psychtropic medication for control of behavior
problems in retarded persons, including sterotypies. Despite its wide
spread use, a number of questions remain concerning thioridazine's efficacy
and the sequalae of its long term administration. This proposal will
investigate how thioridazine affects the stereotypies in institutionalized
mentally retarded persons. One study will investigate the effect of
thioridazine withdrawal in clients who have been maintained on the drug and
who are scheduled to be withdrawn. This experiment will also determine how
environmental challenges affect withdrawal emergent symptons. A second
study will examine the effects of both acute and chronic administration of
thioridazine on stereotyped movements, including their rhythmical
properties. A third study will investigate the interaction of
pharmacotherapy with behavior management procedures. Data are presented to
show that the actions of thioradazine may be due primarily to metabolites
rather than the parent compound. A major strength of these studies are
planned that will parallel the clinical studies. The animal studies will
be done in hamsters, rather than rats, as preliminary data demonstrate that
hamsters metabolize theoridazine in a way similar to that seen in humans.
Thus, hamsters should provide a better model for pharmacodynamic studies
with thioridazine. Chronic and acute drug effects, in combination with
testing for effects of environmental challenges during withdrawal, will
provide important animal data relevant to the interpretation of the
clinical studies.
StatusFinished
Effective start/end date7/1/826/30/87

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Thioridazine
Stereotyped Behavior
Cricetinae
Stereotypic Movement Disorder
Pharmaceutical Preparations
Antipsychotic Agents
Head