Arthur K. Cho, Ph.D., Emeritus
acho@mednet.ucla.edu
Research Interest:
Molecular & Medical Pharmacology
Our laboratory utilizes chemical approaches to conduct research in drug metabolism and neuropharmacology. Drug metabolism studies investigate mechanisms of oxidation of foreign compounds by cytochrome P450, an enzyme system capable of oxidizing the carbon atom of a variety of functional groups including ethers, olefins and amines. Since many of the products of this system are pharmacologically or toxicologically active, their formation is important in understanding drug action. The laboratory is also studying the action of central nervous stimulants related to amphetamine. These compounds affect dopaminergic and serotonergic neurons and stimulate the postsynaptic receptor. These studies have used in vivo microdialysis and pharmacokinetic approaches to understand drug action in intact organisms.
Publications:
Chu T, Kumagai Y, DiStefano EW, Cho AK (1996) Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depiction. Biochem Pharmacol 51: 789-796.
Lin L-Y, Fujimoto M, DiStevano EW, Schmitz DA, Jayashinghe A, Cho AK (1996) Selective mechanism based inactivation of rat CYP2D by 4-allyloxymethamphetamine. J Pharmacol Expt Ther 277: 595-603.
Yamada H, Shiiyama S, Soejima-Ohkuma T, Honda S, Kumagai Y, Cho AK, Oguri K, Yoshimura H (1997) Deamination of amphetamines by cytochromes P450: Studies on substrate specificity and regioselectivity with microsomes and purified CYP2C subfamily isozymes. J Toxicol Sci 22: 67-74.
Lin LY, DiStefano EW, Schmitz DA, Hsu L, Ellis SW, Lennard MS, Tucker GT, Cho AK (1997) Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 25(9): 1059-1064.
Kuczenski R, Melega WP, Cho AK, Segal DS (1997) Extracellular dopamine and amphetamine after systemic amphetamine administration: Comparison to the behavioral response. J Pharmacol Expt Ther 282: 591-596.
Narimatsu S, Arai T, Watanabe T, Masubuchi Y, Horie T, Suzuki T, Ishikawa T, Tsutsui M, Kumagai Y, Cho AK (1997) Covalent binding of a reactive metabolite derived from propranolol and its active metabolite 4-hydroxypropranolol to hepatic microsomal proteins of the rat. Chem Res Toxicol 10(3): 289-295.
Wang MY, Sheu BJ, Berger TW, Young WC, Cho AK (1998) Architecture and design of 1-D enhanced cellular neural network processors for signal detection. Analog Integrated Circuits and Signal Processing 15: 277-290.
Melega WP, Cho AK, Schmitz D, Kuczenski R, Segal DS (1999) l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo deprenyl-derived l-methamphetamine. J Pharmacol Expt Ther 288: 752-758.
Cho AK, Melega WP, Kuczenski R, Segal DS, Schmitz DA (1999) Caudate-putamen dopamine and stereotype response profiles after intravenous and subcutaneous amphetamine. Synapse 31: 125-133.
Cho AK, Naraimatsu S, Kumagai Y (1999) Metabolism of drugs of abuse by cytochromes P450. Addiction Biology (in press):.
Cho,AK, Melega, WP, Kuczenski, R, and Segal, DS. (2001) The Relevance of Pharmacokinetic Parameters in Animal Models of Methamphetamine Abuse. Synapse 39: 161-166.
Cho, A. K., Melega, W. P. (2001) Patterns of methamphetamine abuse and their consequences. Journal of Addictive Diseases 21: 21-34.
Narimatsu, S., Arai, T., Masubuchi, Y., Horie, T., Hosokawa, M., Ueno, K., Kataoka, H., Yamamoto, S., Ishikawa, T., Cho, A. K. (2001) Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol. Biol Pharm Bull 24: 988-94.
Ost, T. W., Munro, A. W., Mowat, C. G., Taylor, P. R., Pesseguiero, A., Fulco, A. J., Cho, A. K., Cheesman, M. A., Walkinshaw, M. D., Chapman, S. K. (2001) Structural and spectroscopic analysis of the F393H mutant of flavocytochrome P450 BM3. Biochemistry 40: 13430-8.