Abstract
Adult rats more than 9-10 weeks old are more susceptible to neurointoxication by p-bromophenylacetylurea than young, more actively growing rats. There is no difference in sensitivity between the sexes.
Partial hepatectomy and damaging the liver with carbon tetrachloride before administering pBPAU are procedures which enhance the degree of neurotoxicity. These studies suggest that the substance is toxic per se, and that it is probably detoxicated by the liver.
Animals treated with sodium phenobarbital both before giving pBPAU and afterwards showed a slightly increased degree of neurointoxication. Pretreatment only with sodium phenobarbital before giving pBPAU did not alter the degree of neurotoxicity. This suggests that the liver microsomal enzymes induced by phenobarbital do not play a direct role in the hepatic metabolism of pBPAU.
pBPAU is not an inhibitor of acetylcholine acetyl-hydrolase (EC No. 3.1.1.7) or benzoylcholine hydrolase (EC No. 3.1.1.9).
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Selected References
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- Buttar H. S., Tyrrell D. L., Taylor J. D. Effect of tri-o-cresyl phosphate, tri-o-cresyl thiophosphate and 2-(o-cresyl)-4H :1:3:2 benzodioxaphosphoran-2-one on pentobarbital induced sleeping time in mice. Arch Int Pharmacodyn Ther. 1968 Apr;172(2):373–379. [PubMed] [Google Scholar]
- Cavanagh J. B., Chen F. C., Kyu M. H., Ridley A. The experimental neuropathy in rats caused by p-bromophenylacetylurea. J Neurol Neurosurg Psychiatry. 1968 Oct;31(5):471–478. doi: 10.1136/jnnp.31.5.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
- DIEZEL P. B., QUADBECK G. [Nerve injury caused by p-bromophenylacetylurea]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1960;238:534–541. [PubMed] [Google Scholar]
- ETO M., CASIDA J. E., ETO T. Hydroxylation and cyclization reactions involved in the metabolism of tri-o-cresyl phosphate. Biochem Pharmacol. 1962 Apr-May;11:337–352. doi: 10.1016/0006-2952(62)90056-4. [DOI] [PubMed] [Google Scholar]
- EVERETT G. M., RICHARDS R. K. Pharmacological studies of phenacetylurea (phenurone) an anticonvulsant drug. J Pharmacol Exp Ther. 1952 Nov;106(3):303–313. [PubMed] [Google Scholar]
- Lasek R. J. Axonal transport of proteins in dorsal root ganglion cells of the growing cat: A comparison of growing and mature neurons. Brain Res. 1970 May 20;20(1):121–126. doi: 10.1016/0006-8993(70)90160-5. [DOI] [PubMed] [Google Scholar]
- MENDEL B., MYERS D. K. Pseudocholinesterase of brain. Nature. 1952 Nov 29;170(4335):928–929. doi: 10.1038/170928b0. [DOI] [PubMed] [Google Scholar]
- Tatsumi K., Yoshihara S., Yoshimura H., Tsukamoto H. Metabolism of drugs. 63. The metabolic fate of 14C-phenacetylurea (phenurone) in mice. Biochem Pharmacol. 1969 Feb;18(2):365–372. doi: 10.1016/0006-2952(69)90214-7. [DOI] [PubMed] [Google Scholar]
- WEAVER L. C., SWINYARD E. A., GOODMAN L. S. Effects of liver injury and nephrectomy on the anticonvulsant activity of phenacemide. Proc Soc Exp Biol Med. 1952 Aug-Sep;80(4):744–746. doi: 10.3181/00379727-80-19749. [DOI] [PubMed] [Google Scholar]