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. The infrared (IR) and Raman spectra of the two crystal forms were significantly different, and their complementary nature was shown from the differences in peak intensities. Solid-state 13C-NMR data of the polymorphs showed only minor differences between the two forms. When viewed on the molecular level through the use of vibrational and NMR spectroscopies, the conformation of the molecule in the two polymorphs appears to be roughly equivalent. The magnitude of the spectral differences of the two polymorphs is, however, consistent with those that can be expected for two crystal forms that have resulted from different modes of packing, as caused by the solvent environment.
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http://dx.doi.org/10.1016/0731-7085(94)e0002-i | DOI Listing |
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.
View Article and Find Full Text PDFJ 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 PDFPharmacol Biochem Behav
March 1994
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322-3090.
DuP 747, trans-3,4-dichloro-N-methyl-N-[2-(pyrrolidin-1-yl)-1,2,3,4- tetrahydronaphthalen-1-yl]benzeacetamide methanesfonate, is a recently synthesized analgesic drug that binds with high affinity and selectivity to the kappa-opioid receptor. In order to determine if DuP 747 has kappa-like discriminative effects it was tested for stimulus generalization in rats trained to discriminate between SC injections of saline and 3.0 mg/kg of spiradoline, a potent kappa-opioid agonist.
View Article and Find Full Text PDFJ 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.
View Article and Find Full Text PDFPharm 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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