Accession Number:

AD0648537

Title:

TOXICOLOGY OF BORON HYDRIDES-STUDIES OF ALTERATIONS IN TISSUE AMINES BY TOXIC DECABORANE-14 (B10H14) AND PENTABORANE-9 (B5H9) AS MODIFIED BY HYDRAZINES AND PROPYNYLAMINES.

Descriptive Note:

Rept. for Oct 63-Mar 66,

Corporate Author:

SCHOOL OF AEROSPACE MEDICINE BROOKS AFB TEX

Personal Author(s):

Report Date:

1966-12-01

Pagination or Media Count:

17.0

Abstract:

Investigations of the influence of the toxic boron hydrides, decaborane-14 and pentaborane-9, on biogenic amine metabolism were undertaken to assist in the elucidation of the toxic mechanisms and sites of action of boron hydrides in animals. Brain and heart tissue serotonin and norepinephrine were found to be significantly depleted after treatment of test subjects with the boron hydrides. The testing of a number of potential antidotes for the treatment of the toxic symptoms and biogenic amine changes due to exposures to boron hydrides has resulted in the discovery of several new antidotal drugs for the toxic effects of decaborane-14. Pargyline N-methyl-N-benzyl-2-propynylamine, a potent nonhydrazide monoamine oxidase MAO inhibitor, provides protection against the depletion of rat brain and heart norepinephrine, as well as the reserpine-like sedation and ataxia observed in decaborane-intoxicated rats. In contrast, several close analogs of pargyline do not protect against the depletion of tissue norepinephrine due to decaborane poisoning. JB-516 1-phenyl-2-hydrazinopropane, a potent hydrazine-related MAO inhibitor, greatly potentiates the toxic effects of decaborane-14, as does iproniazid 1-isonicotinyl-2-isopropylhydrazine. Doses of the B6-vitamin pyridoxine also appear to counteract the toxic effects of decaborane-14. Monoamine oxidase inhibition and elevation of tissue amines per se by a drug do not appear to be required properties for the drug to decrease or eliminate the toxic actions of boron hydrides. Followup studies, which include investigations of the mode of action of pargyline and pyridoxine as protective agents in boron hydride - intoxicated animals, are in progress. Author

Subject Categories:

  • Toxicology
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE