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Initial human safety and tolerance study of a GABA uptake inhibitor, Cl‐966: Potential role of GABA as a mediator in the pathogenesis of schizophrenia and mania
Author(s) -
Sedman Allen J.,
Gilmet Gregory P.,
Sayed Albert J.,
Posvar Edward L.
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430210309
Subject(s) - mediator , mania , schizophrenia (object oriented programming) , medicine , pathogenesis , dopaminergic , psychology , pharmacology , bipolar disorder , lithium (medication) , psychiatry , dopamine
An initial double‐blind, placebo‐controlled safety and tolerance study of single doses of a GABA uptake inhibitor (CI‐966) being developed for the treatment of epilepsy was conducted in healthy volunteers. Drug doses of 1 to 10 mg were well tolerated. A volunteer who received 25 mg of CI‐966 developed transient short‐ and long‐term memory deficits. Both volunteers following administration of 50 mg drug doses presented with a constellation of physical and mental disturbances. Physical abnormalities including tremor, myoclonus, increased muscle rigidity, cogwheeling, and short‐ and long‐term memory impairment of 12–24 hr duration were observed. In addition, striking psychiatric symptoms of many days' duration resembling those seen in patients with mania and schizophrenia were evident. These findings suggest that GABA may modulate memory and dopaminergic pathways responsible for posture and muscle control. In addition, GABA may be a potentially important mediator in the pathogenesis of schizophrenia and mania.