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J J Ryan

Publications and source records attributed to J J Ryan.

9 recordsLinked to original sources
PubMed1979

Novel application of proton nuclear magnetic resonance spectroscopy in the identification of 2'-chloronordiazepam metabolites in the dog.

The only metabolite of 2'-chloronordiazepam, 7-chloro-1,3-dihydro-5-(2'-chlorophenyl)-2H-1,4-benzodiazepin-2-one (1), previously identified in the dog is lorazepam (2), which is a product of 3-hydroxylation. Two phenolic metabolites (3 and 4) in the dog corresponding to 4'-hydroxylation of the 5-phenyl ring and 9-hydroxylation of the fused benzene ring, respectively, have now been identified. The structure of the 9-hydroxy isomer 4 is deduced simply from the observed NMR spectral AB (J meta = 2.5 Hz) pattern of the protons of the fused benzene ring. In contrast, since a 2'-chloro substituent is present on the 5-phenyl ring of the parent drug, the usual method of recognizing 4'-hydroxylation of this ring by observation of AA'BB' multiplets in the proton nuclear magnetic resonance (1H NMR) spectra is inapplicable. Hence, a novel method is introduced to identify the 4'-hydroxy isomer 3, based on attributing different sets of NMR substituent effect parameters to hydroxyl groups, depending on whether these groups are meta or para to the benzodiazepinimine function. The urinary plus fecal excretion of 2-4 by one dog given in a single oral 10 mg/kg dose of 14C-labeled 1 amounted to 20, 5, and 7% of the dose, respectively; the urinary metabolites were excreted predominantly as conjugates of glucuronic acid and/or sulfate.

Animals↗
PubMed1976

Effects of kainic acid, a cyclic analogue of glutamic acid, on cyclic nucleotide accumulation in slices of rat cerebellum.

The concentration of cyclic AMP (cAMP) and cyclic GMP (cGMP) in slices of rat cerebellum was increased markedly in the presence of 100 muM kainic acid, a cyclic analogue of glutamic acid. No acitvity was detected in other brain areas at various dosed or incubation times. Ksainic acid was significantly more potent than glutamic acid and other glutamate-like compounds. The increases in cAMP and cGMP could be differentially inhibited with theophylline or cocaine respectively, but both systems required calcium. Compounds similar in structure to kainic acid or glutamate did not block the effects of kainic acid.

Animals↗