PHARMACOLOGICAL ACTIVITY OF 5‐PHENYL‐1: 3: 4‐THIADIAZOLE (L 1538), 2‐AMINO‐5‐PHENYL‐1: 3: 4‐THIADIAZOLE (L 1460) AND 2‐AMINO‐5‐(2‐THIENYL)‐1: 3: 4‐THIADIAZOLE (L 1458)

Abstract

The pharmacological actions of 5-phenyl-1: 3: 4-thiadiazole (L 1538), 2-amino-5-phenyl-1: 3: 4-thiadiazole (L 1460) and 2-amino-5-(2′-thienyl)-1: 3: 4-thiadiazole (L 1458) have been studied and compared with those of other muscular relaxant drugs. The three compounds have paralysing effects in mice, rats, cats, and dogs. They block the tonic component of maximal electroshock seizures and protect against strychnine, though not against leptazol-induced convulsions in mice. Like other centrally acting paralysing drugs, they depress spinal polysynaptic transmission in doses which leave monosynaptic transmission relatively unaffected. The rigidity of the decerebrate cat is reduced but not always abolished. The compounds do not induce synchronization in epidural electroencephalogram recordings. In doses not greatly affecting muscular tone and spontaneous activity, they prolong the hypnotic effects of pentobarbitone and other barbiturates in mice. Autonomic functions are only slightly affected. The similar actions of substituted thiadiazoles and 2-amino-benzothiazoles confirm a previous hypothesis that pharmacological equivalence may result either from condensing heterocyclic nuclei with aromatic nuclei or from introducing aryl substituents into them.