Ventilatory effects of fourth cerebroventricular infusions of morphine-6- or morphine-3-glucuronide in the awake dog.
The ventilatory effects of morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) were evaluated in awake dogs (n = 10). A fourth ventricle to cisterna magna perfusion (VCP) system was used for drug administration. This permitted a direct comparison of the dose/ventilatory response characteristics of these morphine metabolites to each other and to morphine and obviated the need to consider the blood-brain barrier delay that would complicate analysis of systemic dose versus ventilatory response relationships among these drugs. The dose/response pattern for morphine was taken from an earlier study in unanesthetized dogs where the identical mode of drug delivery as in the present report was employed. Morphine-3-glucuronide caused, if anything, a ventilatory stimulation (decreased PaCO2 and increased CO2 responsiveness) at the highest infusate concentration studied (50 micrograms/ml) and no significant ventilatory effects at infusate concentrations at or below 10 micrograms/ml. On the other hand, M-6-G produced a profound dose-dependent ventilatory depression. Significant increases in PaCO2 and diminution of CO2 responsiveness were observed even at the lowest infusate concentration evaluated (0.1 microgram/ml). When compared to morphine, M-6-G was found to be about five to ten times more potent as a ventilatory depressant drug. These results imply that M-6-G may play a significant role in the ventilatory depression accompanying systemic morphine administration.
Pelligrino
D A
DA
Department of Anesthesiology, Michael Reese Hospital and Medical Center, Chicago, Illinois 60616.
Riegler
F X
FX
Albrecht
R F
RF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D013268:Stimulation, Chemical
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; C018108:morphine-3-glucuronide