PHARMACOLOGICAL PROPERTIES OF BENZAZOLES. II. SITES OF ACTION IN THE CENTRAL NERVOUS SYSTEM

¹ Traverse City State Hospital, Traverse City, Michigan
² Department of Pharmacology, Universily of Illinois College of Medicine, Chicago 12, Illinois

A series of 2-aminobenzothiazoles have been studied in cats for their sites of action in the cerebrospinal axis from the brain stem to the lumbrosacral level of the spinal cord. Their action has been compared to that of mephenesin and benzimidazole.

1. All of the compounds studied have, like mephenesin and benzimidazole, a predominant depressant effect on spinal interneurons. Selective depression of contralatenal sciatic nerve facilitation of the patellar reflex and depression of polysynaptic arc potentials recorded from ventral roots supported this view.

2. Inhibition of interneuronal circuits was also demonstrated by depression of reticulospinal pathways and by relaxation of spastic and decerebrate animals.

3. While 2-aminobenzothiazole had a potency equal to that of mephenesin, substitutions at position 6 doubled the potency and substitutions in the 4 and 7 position tripled it. The position of the substitution rather than the radical (methyl, ethyl, or chloro) involved, appeared to be more important in detenmining the relative potency of these compounds.

4. The compounds with substitutions at position 4 showed some stimulatory action. Monosynaptic arc potentials were enchanced by these compounds while compounds substituted at position 6 showed no such action.