Add time:09/30/2019         Source:sciencedirect.com

The D'Amour-Smith method has been used in rats to study the rate and degree of analgetic tolerance developed when narcotic agents were given with phenothiazine derivatives once daily over a 9-week period. Dosages of the phenothiazines were selected that initially gave approximately the same increase in the analgetic response to each of the analgetic drugs used. Analgetic responses were measured at biweekly intervals and again on the third, seventh, and fourteenth day of withdrawal. No tolerance developed to saline, chlorpromazine, prochlorperazine, or thioperazine. Analgetic tolerance developed most rapidly and to greatest degree with morphine, less with meperidine and raceoramide (SKF dl-5137), and least with phenazocine (cas 127-35-5). Preinjection of the phenothiazines before the analgetic drugs, significantly decreased the rate of development and the degree of analgetic tolerance and hastened recovery during withdrawal. The greatest effect on analgetic tolerance modification was observed for chlorpromazine, next for thioperazine, and least for prochlorperazine.

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