Characterization of the Chemical Constitution and Profile of Pharmacological Activity of PGBx.
Abstract
PGB sub x, a synthetic polymeric derivative prostaglandin PGB sub 1, was examined by various chromatographic techniques, including thin layer, paper and high performance liquid chromatography. Fractions obtained from the separation methods were tested in the bioassay based on restoration of oxidative phosphorylation in aged mitochondria. Some separation of activity was observed but no fractions were devoid of it. The PGB sub x mixture is highly complex containing very similar components based on polarity characteristics. Studies were made to shorten the synthetic sequence to PGB sub x, with concentration on the synthesis of 15-keto-PGB sub 1 from benzalacetone. Seven of the eleven steps have been completed. Pharmacological testing of PGB sub x was evaluated as affecting vasomotor tone and heart rate in: (a) conscious unrestrained rats, (b) adrenalectomized (ADX) pithed rates with exogenous norepinephrine, and (c) ADX and pithed rates subjected to segmental cord stimulation. PGB sub x had no significant effect on B.P. or heart rate in (a). PGB sub x reduced the pressor response to electrical excitation of the cord in a time-dependent manner, and inhibited norepinephrine-induced pressor effects, but to a lesser degree. PGB sub 1 and PGE sub 1 produced short-lived augmentation and inhibition, respectively, of the pressor response. PGB sub x inhibition is believed not to be acting by the blockage of adrenergic receptors but by interference with sympathetic nerve functions. (Author)
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 30, 1980
- Accession Number
- ADA084769
Entities
People
- Allan M. Burkman
- Duane D Miller
- Raymond W. Doskotch
Organizations
- Ohio State University