Canadian Journal of Anesthesia, Vol 12, 137-153, Copyright © 1965 by Canadian Anesthesiologists' Society

Effect of Catecholamine Precursors and Phenylethylamines on Spontaneous Activity and on the Response to Methohexital Anaesthesia

¹ Department of Anesthesiology, State University of New York, Upstate Medical Center, Syracuse, New York, 13210

Adrenergic arousal reactions have been shown to Occur by behavioural responses as well as by changes in the electroencephalogram due to stimulation of the ascending sensory receptors in the reticular activating system. There is good evidence that the arousal response is not due to the vasopressor action of epinephrine, although clinical observations with most vasopressor drugs point to such an explanation. Local vascular changes in the brain which are not necessarily reflected in the general circulation have been suggested and demonstrated as a likely explanation for psychomotor activation by epinephrine.

The precursors of epinephrine also seem to play a role in the control of alertness and motor functions. The negative aspect of this idea explains in part the decrease in spontaneous activity and depression of psychomotor activity in reponse to reserpine administration. The question of whether or not phenylalanine derivatives can themselves produce awakening reactions has been studied to a limited extent. A very large dose of l-dopa does produce an awakening response in reserpinized mice. To a less extent, m-tyrosine appears to have a similar effect. The two isomers of dopa and o-tyrosine, however, are devoid of the activating property, Other epinephrine precursors, except norepinephrine, are virtually mert.

This study was devised to determine whether the epinephrine precursors (phenylalanine derivatives) as well as tyramine, methyldopate, and amphetamine produce an alerting response and increased motor in rats deprived of extrinsic stimulation. Before and following intraperitoneal injection of the test drugs, rats were placed individually in a transparent box that was mounted on a weighing scale and attached to a recording apparatus which inscribed on paper even the slightest movement of the rat. All of the catecholamine precursors studied produced some alterations in the spontaneous activity of the rats dl-Dopa caused the greatest increase in motor activity, the reaction being quantitatively similar to that seen with amphetamine l-Tyrosine, m-tyrosine, tyramine, and dopamine produced a peculiar effect on the rats—they appeared as if they were under the influence of a potent sedative, but they had numerous aperiodic startle movements which, on the recording, appeared as if they had a substanital alerting reaction. Although the activity tracing for amphetamine and dopa appeared similar, the rats appeared quite different on direct observation. Dopa produced an increase in motor activity which appeared co-ordinated and purposeful, whereas amphetamine caused an increase in co-ordinated movements but there was also a generalized increase in body movement that resembled muscle trembling, similar to that seen in nicotine poisoning.

The effect of m-tyrosine, dopa, methyldopate, and amphetamine given 20 minutes before or simultaneously with methohexital anaesthesia revealed, contrary to expectation, that hypnosis was uniformly prolonged with each, except with amphetamine. These data were interpreted as contradicting the opinion that the psychomotor effects of the catecholamine precursors can be considered in the same category as epinephrine. It was also evident that amphetamine acts quite differently from the precursors of epinephrine, whereas methyldopate either suppresses motor activity or has very little activity in this regard.

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Supported in part by USPHS Grant NB-03809-03