Beneficial action of a new opiate antagonist (Win 44,441-3) in hemorrhagic shock.
The new opiate antagonist Win 44,441-3 (-)-isomer was infused intravenously in cats at a rate of 2 mg . kg-1 . h-1 to determine its effect in hemorrhagic shock. Hemorrhaged cats treated with Win 44,441-3 maintained post reinfusion mean arterial blood pressure (MABP) at a higher value compared to cats receiving only the vehicle. Final MABP was 70 +/- 11 mm Hg for cats receiving vehicle compared to 103 +/- 7 mm Hg for cats receiving Win 44,441-3. These values represent 60 +/- 9% and 85 +/- 6% of initial MABP for the vehicle- and Win 44,441-3-treated cats respectively. Win 44,441-2 (+)-isomer, the inactive stereoisomer of Win 44,441-3, was also infused at 2 mg . kg-1 . h-1 in cats subjected to hemorrhagic shock. The final pressure in this group was 72 +/- 8 mm Hg which is 61 +/- 8% of the initial pressure for this group. Win 44,441-3 and Win 44,441-2 were both ineffective in moderating increases in circulating lysosomal hydrolase activity in shocked cats. Neither isomer stabilized lysosomal membranes or retarded proteolysis in vitro. Plasma myocardial depressant factor was significantly reduced by the opiate antagonist, Win 44,441-3 during shock. Our results show that the systemic infusion of an opiate antagonist improves the hemodynamic state of cats subjected to hemorrhagic shock while the (+)-isomer which lacks opiate antagonist activity produces no such improvement.
D000818:Animals; D001392:Azocines; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D002415:Cats; D008099:Liver / Q000378:metabolism; D008297:Male; D009019:Morphinans / Q000627:therapeutic use*; D009201:Myocardial Depressant Factor / Q000097:blood; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D011957:Receptors, Opioid / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D001392:Azocines; D001575:Benzomorphans; D009019:Morphinans; D009201:Myocardial Depressant Factor; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D002403:Cathepsins; D002402:Cathepsin D; C035969:quadazocine