The Ca2+ channel agonist Bay K 8644 induces central respiratory depression in cats, an effect blocked by naloxone.

We analyzed the respiratory effects induced by the Ca2+ channel agonist Bay K 8644 and its enantiomers, Bay R 5417 and Bay R 4407, applied to the ventral medullary surface of cats. Bay K 8644 (10 to 100 micrograms) and Bay R 5417 (50 to 200 micrograms) elicited a dose-dependent respiratory depression. Naloxone (0.1 mg/kg), but not D-naloxone, reversed these effects, indicating that an endogenous opioid mechanism was involved. Bay R 4407 (100 micrograms) was ineffective. The respiratory depressant effects induced by Bay K 8644 and its (-) enantiomer were a consequence of their agonist properties on the L-type Ca2+ channel, since (1) the activity of Bay K 8644 was stereospecific, and (2) nimodipine prevented the effect. We suggest that potent activation of Ca2+ channels or other mechanisms by high doses of Ca2+ agonists elicits the release of endogenous opioid peptides in medullary respiration-related structures.