COMPARATIVE ACTIONS OF ANALGESIC, HYPNOTIC AND PARALYTIC AGENTS ON HINDLIMB REFLEXES IN CHRONIC SPINAL DOGS

¹ National Research Council, U. S. P. H. S., Sloan-Kettering Institute for Cancer Research, New York, N. Y.
² National Institute of Mental Health, National Institutes of Health, Public Health Service, Research Branch, U. S. Public Health Service Hospital, Lexington, Kentucky
³ Department of Pharmacology, University of Michigan, Ann Arbor, Mich.

1. Characteristic changes in the pattern of hindlimb reflexes in chronic spinal dogs are observed after administration of potent analgesic (morphine and methadone), hypnotic (thiopental and pentobarbital) and paralytic (mephenesin and benzimidazole) agents.

2. When the ipsilateral flexor, crossed extensor and Philippson's reflexes were depressed markedly by adequate doses of these drugs, the ipsilateral extensor thrusts were enhanced by the analgesics and depressed by the other agents. Concomitantly, the knee jerks were enhanced by the paralytic compounds, depressed by the hypnotics and were affected slightly and variably by the analgesics under the conditions of our experiments.

3. After administration of 100 mgm./kgm. of morphine, the ipsilateral flexor reflex was depressed and the ipsilateral extensor thrust, enhanced. These effects persisted for several days, after which the ipsilateral flexor reflex became hyperactive, while the ipsilateral extensor thrust was reduced in magnitude. These "rebound" effects were partially reversed by an additional dose of as little as 1 mgm./kgm. of morphine. Such changes resemble those which occur in the hindlimbs of chronic spinal dogs after abrupt withdrawal of morphine following a period of addiction to smaller doses of the drug.

4. The specificity of the changes in pattern of hindlimb reflexes in chronic spinal dogs, which are produced by single doses of analgesic, hypnotic and paralytic agents may serve as a more reliable basis for classifying new compounds than the use of any single reflex, either in intact or in spinal animals.

5. The proper place of studies on spinal animals in research on the mechanisms of drug action is discussed.

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