Nithiananda Chatterjie

Narcotic Antagonist Activity of Several Metabolites of Naloxone and Naltrexone Tested in Morphine Dependent Mice

Summary A rabbit liver enzyme system was used to produce the 6β-OH reduced metabolites of naloxone and naltrexone. GC analysis indicated the presence of some 6α-0H metabolite in these samples. The narcotic antagonist activity of these 6β-OH metabolite samples were compared to nalox-one, naltrexone and standard 6α-OH nalox-one (EN 2265A) and 6α-OH naltrexone (EN 2260A) using the jumping response of morphine pellet implanted mice. For the nal-oxone series, the potencies were: Naloxone > EN 2265A > 6β-OH naloxone. For the naltrexone series: Naltrexone > EN 2260A > 6β-OH naltrexone. The low potency of the reduced metabolites and the rapid onset of action of the parent compounds militate against the formation of these metabolites contributing substantially to the overall narcotic antagonist action of the parent compounds. The authors wish to acknowledge the excellent technical assistance of Miss Ann Klecker. Dr. Harold Blumberg of Endo Laboratories generously provided the naloxone, naltrexone, EN 2265 and EN 2260.

Simultaneous determination of acetylmethanol and its active biotransformation products in human biofluids

A method employing solvent extraction and gas-liquid chromatography has been developed for the quantitative determination of acetylmethadol simultaneously with its two major biotransformation products, noracetylmethadol and dinoracetylmethadol. Noracetylmethadol and dinoracetylmethadol are analyzed following their conversion to the corresponding amides. The amide structure is confirmed by the use of chemical ionization mass spectroscopy and infrared spectroscopy. The method can be used to determine the concentration of acetylmethadol and these compounds in plasma samples from acetylmethadol maintenance subjects. Methadol and normethadol do not attain neasurable plasma levels. Urine contains predominantly noracetylmethadol and dinoracetylmethadol. Evidence was also obtained for the urinary excretion of acetylmethadol, methadol and normethadol. A mean quantity equal to 28% of the administered dose was excreted in the urine of a 48-h dosing interval as acetylmethadol and metabolites.

Synthesis of 2-Aminomorphine and 2-Aminocodeine. Reduction of Aromatic Nitro Groups with Formamidinesulfinic Acid

Abstract Our interest in the stereoselective reduction2 of the carbonyl groups of various oxymorphone derivatives with formamidinesulfinic acid (FSA) led to a result indicating that dihydrocodeinone3 underwent ring-oxygen scission4 under the conditions of reduction with this reagent. This observation4 has prompted interest and speculation as to the scope and mechanism of this reaction by others5, as well as ourselves.