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 mumol) 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.
Dierssen
M
M
Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain.
Ruiz
F
F
Flórez
J
J
Hurlé
M A
MA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002415:Cats; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects* / Q000502:physiology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D017409:Sufentanil
D015220:Calcium Channels; D012462:Saline Solution, Hypertonic; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D017409:Sufentanil; D005283:Fentanyl