N-allylnormetazocine: hemodynamic actions and inhibition of leucine-enkephalin hemodynamic activity in conscious dogs.
The hemodynamic actions of dl-, d-, and l-N-allylnormetazocine (NANM) were examined. dl-NANM significantly increased heart rate and systemic arterial pressure in a dose-dependent manner. Naloxone (1 mg/kg) inhibited the hemodynamic actions of 0.5 mg/kg dl-NANM. At a dose of 0.25 mg/kg, l-NANM, but not d-NANM, significantly increased heart rate and mean arterial pressure. The effects of l-NANM were blocked by naloxone but not by naloxone-methylbromide, indicating that the opiate effects are mediated by receptors located in the central nervous system. At a higher dose (0.5 mg/kg), d-NANM consistently produced small increases in heart rate and blood pressure which were statistically significant. The hemodynamic actions of Leu-enkephalin were inhibited by pretreatment with dl-NANM and l-NANM but not d-NANM. These results indicate that NANM has opiate hemodynamic activity which resides with the levorotary isomer. Dextrorotary isomer activity is nonopiate or possibly nonspecific. Furthermore, there appears to be a inhibitory interaction between NANM-opiate and enkephalin hemodynamic actions. This suggests that NANM-opiate receptors may be involved in modulation of the hemodynamic response to circulating enkephalins.
Given
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MB
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
Sander
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GE
Lowe
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Giles
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TD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004743:Enkephalin, Leucine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013237:Stereoisomerism
D009270:Naloxone; D004743:Enkephalin, Leucine; C012134:SK&F 10047; D010620:Phenazocine