| Popis: |
The toxic and lethal effects of piminodine and Win 13,797 were studied in mice, dogs, and monkeys. The analgesic actions of both drugs were tested in mice and rats and were found to be more potent than morphine. Vascular studies on pimincdine and Win 13,797 have shown peripheral vasodilation and acute vascular tolerance to the hypotensive effect in dogs with partial crossed tolerance to morphine. Dogs anesthetized with pentobarbital were sensitive to the respiratory depressant actions of these drugs. Nalorphine readily antagonizes this respiratory depression. Piminodine and Win 13,797 are myocardial depressants on the dog heart-lung preparation and the cat papillary muscle, but only in doses or concentrations much higher than would be used therapeutically. The actions of piminodine and Win 13,797 on the isolated rabbit jejunal segment are minimal. The qualitative actions of piminodine and Win 13,797 on EEG effects in dogs with chronically implanted electrodes were like those of morphine. Quantitatively, Win 13,797 was equipotent to morphine, and piminodine one-half as effective. Studies on single-dose suppression in monkey and primary physical dependence in dogs and monkeys indicate that piminodine and Win 13,797 have high addiction liability at least in these species. Nearly all the administered piminodine or Win 13,797 is altered chemically when injected into dogs. There is no evidence for marked local tissue deposition for either drug. |
