LOCUS OF CENTRAL DEPRESSANT ACTION OF DIAZEPAM

¹ Department of Pharmacology, College of Physicians & Surgeons, Columbia University, New York, New York

Diazepam, a centrally acting skeletal muscle relaxant, has previously been shown to act chiefly at the supraspinal level in midcollicular decerebrate cats. The depressant effect of diazepam (0.05-0.2 mg/kg i.v.) on polysynaptic extensor reflexes in those studies appeared to be nullified by spinal cord transection. Our current experiments, using midcollicular decerebrate cats, further ascertain the supraspinal locus of action of diazepam on the spinal reflexes. First, diazepam, given i.v. (0.1 mg/kg) or into the vertebral artery (0.01 mg/kg), is capable of reducing facilitation and inhibition of the knee jerk caused by electrical stimulation of the mesencephalic reticular facilitatory and the medullary reticular inhibitory systems, respectively. See only, diazepam, given i.v., can cause a stepwise reduction in the spontaneous spike rate of neurons located in the mesencephalic reticular facilitatory system, and simultaneously reduce the polysynaptic extensor reflex. Administration of diazepam into the vertebral artery has the same effect, and the doses required are much smaller (0.005 mg/kg). Latency for onset of drug action is also shorter, 1 sec (vs. 10 sec by i.v. administration). Thus, the brainstem reticular system is the major locus of central nervous system depressant action of diazepam.

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