Bremazocine, [5R-(5,7,8 beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro [4,5]dec-8-yl]-4-benzofuranacetamide (Cl-977), (+-)-trans-3,4-dichloro-N- methyl-(2-(pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetrahydronapth++ +-1-yl benzeneacetamide methanesulfonate (DUP 747), ethylketocyclazocine (EKC), nalorphine, (+/-)-trans-N-methyl-N-[2-(1- pyrrolidnyl)-cyclohexyl]benzo[b]thiophene-4-acetamide (PD117302), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide (U-50,488), (5,7,8 beta)-N-methyl-N[2-(1- pyrrolidinyl), 1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U-69,593) and spiradoline were compared in rhesus monkeys for their discriminative stimulus, analgesic and respiratory effects. Selected compounds also were studied for their binding affinities at mu [[3H](D-Ala2-Me-Phe4,Glyol5)enkephalin], kappa ([3H]U-69,593) and delta [[3H](D-Pen2-D-Pen5) enkephalin], opioid receptors in monkey brain membranes. All compounds substituted completely (> or = 90%) for EKC in monkeys discriminating between EKC and saline, with the exception that DUP 747 produced a maximum of 74% EKC responding. None of the compounds reversed naltrexone responding in morphine-abstinent monkeys; all of the compounds substituted for naltrexone in morphine-treated monkeys discriminating between naltrexone and saline, with the exception that spiradoline produced a maximum of 68% naltrexone responding. Eight compounds produced maximum analgesic effects in a tail withdrawal procedure and quadazocine antagonized these effects; nalorphine did not have analgesic effects, but it antagonized analgesic effects of several other compounds. U-50,488 did not decrease respiratory function, whereas U-69,593 decreased frequency of respiration and volume of respiration to less than 40% of control values; Cl-977, DUP 747, PD117302 and spiradoline had limited effects on respiratory function. Larger doses of each compound increased both respiration and motor activity.
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Further characterization of the discriminative stimulus effects of spiradoline.
Pharmacol Biochem Behav
July 2000
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
The results of a previous study in rats indicated that spiradoline has pharmacologically selective discriminative effects that are mediated by kappa-opioid receptors. However, the training dose, 3.0 mg/kg, increased response latencies, suggesting that it was relatively high.
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J Pharm Biomed Anal
June 1994
DuPont Merck Pharmaceutical Co., Wilmington, DE 19880-0400.
DuP 747, a selective kappa agonist analgesic, was found to have at least two polymorphic forms, and this was confirmed by X-ray powder diffraction. DSC and thermomicroscopic studies indicated the polymorphic pair to be monotropic. Solubility studies suggested the relative stability of the two forms to be similar.
View Article and Find Full Text PDFAssessing spiradoline-like discriminative effects of DuP 747: influence of route of administration.
Pharmacol Biochem Behav
March 1994
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322-3090.
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View Article and Find Full Text PDFComparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities.
J Pharmacol Exp Ther
January 1994
Department of Pharmacology, Louisiana State University Medical Center, New Orleans.
Bremazocine, [5R-(5,7,8 beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro [4,5]dec-8-yl]-4-benzofuranacetamide (Cl-977), (+-)-trans-3,4-dichloro-N- methyl-(2-(pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetrahydronapth++ +-1-yl benzeneacetamide methanesulfonate (DUP 747), ethylketocyclazocine (EKC), nalorphine, (+/-)-trans-N-methyl-N-[2-(1- pyrrolidnyl)-cyclohexyl]benzo[b]thiophene-4-acetamide (PD117302), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide (U-50,488), (5,7,8 beta)-N-methyl-N[2-(1- pyrrolidinyl), 1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U-69,593) and spiradoline were compared in rhesus monkeys for their discriminative stimulus, analgesic and respiratory effects. Selected compounds also were studied for their binding affinities at mu [[3H](D-Ala2-Me-Phe4,Glyol5)enkephalin], kappa ([3H]U-69,593) and delta [[3H](D-Pen2-D-Pen5) enkephalin], opioid receptors in monkey brain membranes. All compounds substituted completely (> or = 90%) for EKC in monkeys discriminating between EKC and saline, with the exception that DUP 747 produced a maximum of 74% EKC responding.
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Pharm Res
June 1992
Du Pont Merck Pharmaceutical Co., Experimental Station, Wilmington, Delaware 19880-0400.
The nonopioid kappa agonist analgesic amine, DuP 747, as a hydrochloride salt exhibited an aqueous solubility of 3 mg/ml. This solubility was insufficient to provide the desired dose in a solution formulation for intramuscular administration. Aqueous solutions of the hydrochloride salt exerted surface activity behavior; however, the critical micellar concentration (CMC) was not reached at the saturation solubility.
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