CONTRADICTORY ACTIONS OF CAFFEINE, CORAMINE, AND METRAZOL

¹ The Department of Pharmacology, Howard University School of Medicine, Washington, D.C.

The results of experiments on rats and rabbits narcotised with barbital and treated with caffeine, coramine, or metrazol reveal the fact that these substances are capable of accentuating the depressant action of the barbiturate under certain conditions.

The barbiturate was administered in single sub-lethal doses. The other substances were given in varying quantities, each dosage unit being slightly below or above the lethal level for normal controls.

Sub-lethal doses of caffeine and coramine administered to the barbitalised rat caused transient arousals, with tremors or mild convulsions at certain dosage levels and the same effects, followed by delayed death in depression, at higher levels. The percentage of recoveries from the combined substances was less than that from caffeine and coramine alone.

Lethal doses of metrazol caused permanent arousal without convulsions at lower dosage levels, permanent arousal with convulsions at higher levels, and convulsions followed by death at still higher levels. The barbitalised rat was able to tolerate large lethal doses of metrazol, indicating a high degree of reciprocal antagonism between barbital and metrazol in that species.

A depressant effect was more in evidence than a stimulatory action with caffeine.

The rat manifests a distinct species intolerance to coramine. It is not a suitable animal on which to make generalisations in comparative studies on coramine.

Normally stimulating doses of coramine and metrazol, administered in single or fractional portions to barbitalised rabbits, caused transitory arousal at certain dosage levels, with death in depression in others; but in every instance coramine or metrazol, when combined with barbital, increased the duration of narcosis over that of the controls, and caused some fatalities.

These studies point to possible danger in the use of these substances indiscriminately in barbiturate depression and emphasise their contraindication in deep barbiturate depression.

We interpret these phenomena as due to a secondary depressant action of caffeine, coramine, and metrazol elicited at certain levels of depression initiated by the barbiturates.