In preclinical studies, 5-imino-2,2,4,4-tetrakis (trifluoromethyl)
Departments of Neurological Research, Neuropsychiatric Examining Service, and Therapeutics, Veterans Adminiotration Outpatient ClinicThe structure of 5-imino-2,2.,4,4-tetrakis (triRuoromethyl) imidazolidine (EXP 338)" is shown in Fig. l,1 Preclinical studies revealed that this preparation is capable of reducing abnormal neural activity by its effect on polysynaptic reRex arcs and to a lesser degree upon monosynaptic circuits in experimental animals. No evidence of peripheral interference with neuromuscular transmission was found.8 Toxicology studies revealed no toxicity which would preclude clinical trial. Subsequently it was given to about 20 patients with neurologic diseases for 1 to 60 days without any apparent alterations in urine or blood. 2 Studies in mice with 14C-Iabeled drug indicated a half-life of 8 hours and that the drug was rapidly absorbed and uniformly distributed. 9 Adverse effects of drowsiness, disorientation, ataxia, and convulsions had followed single doses of 50 to 100 mg. of the test drug given orally.2Received for publication Dec. 19, 1967. Accepted for publication April 9, 1968. ·IND, DuPont, Wilmington. Del.
448A quantitative, non blind evaluation of oral EXP 338 was carried out on 15 pa-