CA2+ CHANNEL MODULATION BY DIHYDROPYRIDINES MODIFIES SUFENTANIL-INDUCED RESPIRATORY DEPRESSION IN CATS

We analyzed the interaction between sufentanil, a selective mu-agonist, and two dihydropyridines, the Ca2+ antagonist, nimodipine, and the Ca2+ agonist, Bay K 8644, on the respiratory actions induced in the brainstem of cats. Drugs were applied topically to the ventral medullary surface. Sufentanil (0.26-26 nmol) consistently induced an immediate and dose-dependent reduction in tidal volume. Respiratory frequency was only depressed by the higher doses of the opiate. Pretreatment with nimodipine (0.19 and 0.38-mu-mol) potentiated the respiratory depression induced by sufentanil (0.26 nmol). The potentiation included both frequency and tidal volume. On the other hand, under the influence of Bay K 8644 (0.28 nmol), the respiratory effect of the opiate (7.8 nmol) was partially antagonized. Our results indicate that modulation of the L-type Ca2+ channels by dihydropyridines modifies sufentanil-induced respiratory depression at the controlling medullary mechanisms of breathing.