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Orphenfldrine was evaluated as a neurospasmolytic agent in 14 patients and as an antitremor agent in 2 patients. Response to single 100 mg. doses was measured 1 and 2 hours after medication, and the effect of maintenance therapy with 100 mg. twice a day was measured weekly for 4 weeks. Orphenadrine appeared to be highly effective in the 1 and 2 hour tests but less effective with sustained treatment. In all instances telemedography showed patients had a higher percentage of favorable responses. Orphenadrine was clearly effective in reducing intention tremor in the 2 patients tested with sustained treatment, but less so in the 1 and 2 hour observations.

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-