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Chemical Compound Review

PERHEXILINE     2-(2,2- dicyclohexylethyl)piperidine

Synonyms: Perhexilene, Perhexilina, Perhexilinum, perhexilline, CHEMBL75880, ...
 
 
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Disease relevance of PERHEXILINE

 

Psychiatry related information on PERHEXILINE

 

High impact information on PERHEXILINE

 

Chemical compound and disease context of PERHEXILINE

 

Biological context of PERHEXILINE

 

Anatomical context of PERHEXILINE

 

Associations of PERHEXILINE with other chemical compounds

 

Gene context of PERHEXILINE

  • CYP2B6, CYP2D6, and CYP3A4 Catalyze the Primary Oxidative Metabolism of Perhexiline Enantiomers by Human Liver Microsomes [24].
  • Perhexiline thus trapped considerable amounts of Tf-R in the internal compartment [25].
  • In contrast, AMPK activators, like perhexiline and oligomycin, produced a significant elevation in heparin-releasable LPL activity [26].
  • However further study is required to clarify the effect of perhexiline on different NADPH oxidase isoforms particularly in the vasculature [27].
  • These data imply that perhexiline inhibits the phagocytic NADPH oxidase directly, and that pig aortic valvular interstitial cells possess a similar enzyme, a conclusion supported by immunohistochemical localisation of the gp91phox subunit in these cells [27].
 

Analytical, diagnostic and therapeutic context of PERHEXILINE

  • Perhexiline-induced lipidosis in the dark Agouti (DA) rat. An animal model of genetically determined neurotoxicity [15].
  • Pharmacotherapy with perhexiline and/or statins may improve platelet responsiveness to NO [28].
  • Drug oxidation was measured using an oxidation phenotyping procedure in four patients with perhexiline liver injury and in 70 patients with chronic liver disease serving as a control group [16].
  • In addition, the effects of perhexiline on atrial and ventricular thresholds to electrical stimulation were recorded, as well as the QRS and QT intervals, sinus rate, and rhythm disorders [29].
  • Dogs pretreated orally with perhexiline, 200 mg/day/14 days, and monitored under anesthesia for 30 hours after ligation of the left anterior descending coronary artery (LAD) had infarct weights of 9.1+/-1.9 g as compared to 15.2+/-1.0 g in paired untreated controls (P less than .02) [19].

References

  1. Perhexiline maleate-induced cirrhosis. Pessayre, D., Bichara, M., Degott, C., Potet, F., Benhamou, J.P., Feldmann, G. Gastroenterology (1979) [Pubmed]
  2. Perhexilene mimicking bronchial carcinoma. Dawkins, K.D., O'Connor, E. Lancet (1978) [Pubmed]
  3. Factors influencing the long-term prognosis of treated patients with variant angina. Waters, D.D., Miller, D.D., Szlachcic, J., Bouchard, A., Méthé, M., Kreeft, J., Théroux, P. Circulation (1983) [Pubmed]
  4. Polyneuropathy with normal metabolism of perhexiline maleate. Jallon, P., Loiseau, P., Orgogozo, J.M., Singlas, E. Ann. Neurol. (1978) [Pubmed]
  5. Activity of bepridil and other anti-anginals on cardiovascular modifications engendered by conditioned anxiety in the dog. Piris, P., Beaughard, M., Cosnier, D., Labrid, C. Archives internationales de pharmacodynamie et de thérapie. (1978) [Pubmed]
  6. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Berson, A., De Beco, V., Lettéron, P., Robin, M.A., Moreau, C., El Kahwaji, J., Verthier, N., Feldmann, G., Fromenty, B., Pessayre, D. Gastroenterology (1998) [Pubmed]
  7. Effects of glucagon, histamine, and perhexiline on the ischemic canine mesenteric circulation. Schwaiger, M., Fondacaro, J.D., Jacobson, E.D. Gastroenterology (1979) [Pubmed]
  8. Inhibition by perhexiline of oxidative phosphorylation and the beta-oxidation of fatty acids: possible role in pseudoalcoholic liver lesions. Deschamps, D., DeBeco, V., Fisch, C., Fromenty, B., Guillouzo, A., Pessayre, D. Hepatology (1994) [Pubmed]
  9. The relative sensitization by acidosis of five calcium blockers in cat papillary muscles. Smith, H.J., Briscoe, M.G. J. Mol. Cell. Cardiol. (1985) [Pubmed]
  10. Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. Kennedy, J.A., Kiosoglous, A.J., Murphy, G.A., Pelle, M.A., Horowitz, J.D. J. Cardiovasc. Pharmacol. (2000) [Pubmed]
  11. Genetically determined differences in drug metabolism as a risk factor in drug toxicity. Eichelbaum, M., Kroemer, H.K., Mikus, G. Toxicol. Lett. (1992) [Pubmed]
  12. Effects of sustained isometric handgrip on ventricular systolic time intervals in patients with ischemic heart disease. Inotropic state of the left ventricle during treatment with perhexiline maleate and with propranolol. Caponnetto, S., Iannetti, M., Pastorini, C., Masperone, M.A., Perugini, P., Oriani, G. Japanese heart journal. (1977) [Pubmed]
  13. Enhancement of ricin A chain immunotoxin activity by perhexiline on established and fresh leukemic cells. Jaffrézou, J.P., Levade, T., Kuhlein, E., Thurneyssen, O., Chiron, M., Grandjean, H., Carrière, D., Laurent, G. Cancer Res. (1990) [Pubmed]
  14. Reversal of acquired resistance to doxorubicin in P388 murine leukemia cells by perhexiline maleate. Ramu, A., Fuks, Z., Gatt, S., Glaubiger, D. Cancer Res. (1984) [Pubmed]
  15. Perhexiline-induced lipidosis in the dark Agouti (DA) rat. An animal model of genetically determined neurotoxicity. Meier, C., Wahllaender, A., Hess, C.W., Preisig, R. Brain (1986) [Pubmed]
  16. Impaired oxidation of debrisoquine in patients with perhexiline liver injury. Morgan, M.Y., Reshef, R., Shah, R.R., Oates, N.S., Smith, R.L., Sherlock, S. Gut (1984) [Pubmed]
  17. Perhexiline during exercise training in coronary heart disease. Teo, K.K., Kelly, J.G., Darby, J.F., Ennis, J.T., Horgan, J.H. Clin. Pharmacol. Ther. (1983) [Pubmed]
  18. Beneficial clinical effects of perhexiline in patients with stable angina pectoris and acute coronary syndromes are associated with potentiation of platelet responsiveness to nitric oxide. Willoughby, S.R., Stewart, S., Chirkov, Y.Y., Kennedy, J.A., Holmes, A.S., Horowitz, J.D. Eur. Heart J. (2002) [Pubmed]
  19. Effects of perhexiline on survival time and infarct size in experimental myocardial infarction. Daniell, H.B., Privitera, P.J., Conradi, S.E., Gaffney, T.E. J. Pharmacol. Exp. Ther. (1977) [Pubmed]
  20. The effects of perhexiline on the sympathetic nervous system. Daniell, H.B., Saelens, D.A., Webb, J.G. J. Pharmacol. Exp. Ther. (1979) [Pubmed]
  21. Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Cole, P.L., Beamer, A.D., McGowan, N., Cantillon, C.O., Benfell, K., Kelly, R.A., Hartley, L.H., Smith, T.W., Antman, E.M. Circulation (1990) [Pubmed]
  22. Polymorphic hydroxylation of perhexiline maleate in man. Cooper, R.G., Evans, D.A., Whibley, E.J. J. Med. Genet. (1984) [Pubmed]
  23. The effect of verapamil and other calcium antagonists on chemotaxis of polymorphonuclear leukocytes. Elferink, J.G., Deierkauf, M. Biochem. Pharmacol. (1984) [Pubmed]
  24. CYP2B6, CYP2D6, and CYP3A4 Catalyze the Primary Oxidative Metabolism of Perhexiline Enantiomers by Human Liver Microsomes. Davies, B.J., Coller, J.K., Somogyi, A.A., Milne, R.W., Sallustio, B.C. Drug Metab. Dispos. (2007) [Pubmed]
  25. Transferrin receptor functions as a signal-transduction molecule for its own recycling via increases in the internal Ca2+ concentration. Sainte-Marie, J., Lafont, V., Pécheur, E.I., Favero, J., Philippot, J.R., Bienvenüe, A. Eur. J. Biochem. (1997) [Pubmed]
  26. The metabolic "switch" AMPK regulates cardiac heparin-releasable lipoprotein lipase. An, D., Pulinilkunnil, T., Qi, D., Ghosh, S., Abrahani, A., Rodrigues, B. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  27. Effect of the anti-anginal agent, perhexiline, on neutrophil, valvular and vascular superoxide formation. Kennedy, J.A., Beck-Oldach, K., McFadden-Lewis, K., Murphy, G.A., Wong, Y.W., Zhang, Y., Horowitz, J.D. Eur. J. Pharmacol. (2006) [Pubmed]
  28. Stable angina and acute coronary syndromes are associated with nitric oxide resistance in platelets. Chirkov, Y.Y., Holmes, A.S., Willoughby, S.R., Stewart, S., Wuttke, R.D., Sage, P.R., Horowitz, J.D. J. Am. Coll. Cardiol. (2001) [Pubmed]
  29. Electrophysiologic properties of perhexiline. Vera, Z., Gray, D.R., Harter, K.W., Janzen, D.A., Massumi, R.A., Mason, D.T. Clin. Pharmacol. Ther. (1975) [Pubmed]
 
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