Cardiovascular and respiratory effects of an opioid kappa agonist ethylketazocine and sigma agonist N-allylnormetazocine in acutely decerebrated dogs.

Effects of opioid kappa agonist ethylketazocine (EKC), sigma agonist (+-)-N-allylnormetazocine (NANM), and naloxone alone and in combination on mean blood pressure (MBP), heart rate (HR), respiratory rate (RR) and minute volume (MV) were studied in acutely decerebrated dogs. EKC (0.5 mg/kg) decreased HR, MBP, RR and MV. Post-EKC NLX increased RR and MV and reversed the bradycardia and hypotension produced by EKC. NANM (1 mg/kg) produced respiratory depression and tachycardia without changing MBP. Post-NANM NLX antagonized tachycardia, increased MBP, however did not significantly change RR and MV. When decerebrate dogs were spinalized at the C-1 level, EKC decreased MBP and HR. These effects were antagonized by NLX. NANM did not change HR but raised MBP in spinalized decerebrate dogs. Since EKC- and NANM-induced cardiovascular and respiratory depression were not observed in conscious intact or chronic spinal dog, it is suggested that: 1) kappaergic system rostral to mesencephalon may play a role in counteracting these depressant effects of EKC; 2) sigma receptor-mediated tachypnea and tachycardia are dissociable; the tachypneic effect may be mediated through higher center while the medulla oblongata is involved in producing tachycardia. These results also suggest that (+-)-NANM probably has several mechanisms of action at several brain sites in producing its effects on respiration and cardiovascular function.