PHARMACOLOGIC STUDIES ON ANALGESICS—VII. SIGNIFICANCE OF THE CALCIUM ION IN MORPHINE ANALGESIA

¹ Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Hotarugaike, Osaka, Japan

In order to determine the significance of calcium in the physiologic function of the central nervous system with reference to the analgesic effect of opiates, the effect of calcium ion on the analgesic responses to morphine, meperidine and ohton was studied, using the methods of electrical stimulation and tail flick in mice. The intracisternal administration of calcium markedly suppressed the analgesic effects of morphine, meperidine and ohton, which were given either subcutaneously or intracisternally. Calcium also antagomzed the established analgesic effects of these drugs. In contrast, decalcifying agents such as ethylenediaminetetraacetic acid·2Na, cyclohexanediaminetetraacetic acid.2Na, sodium citrate and sodium oxalate injected intracistennally enhanced the analgesic effects of morphine, meperidine and ohton, and antagonized the antagonistic effect of calcium on the analgesic response. The calcium complexes of these chelating agents and other cations such as magnesium, barium, strontium, zinc, ferrous, aluminum, potassium and sodium had no analgesic effect themselves, and affected neither the analgesic response to morphine nor the antagonistic action of calcium on the analgesia produced by morphine. These results suggest that calcium in the central nervous system is involved in the mechanism of analgesia produced by opiates.

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