Pharmacogenetics of chlorpromazine and its role in the development of antipsychotic-induced parkinsonism
https://doi.org/10.52667/2712-9179-2021-1-1-11-17
Abstract
Antipsychotics (AP) is a group of psychotropic drugs for the treatment of mental disorders, in particular schizophrenia. In the mid-1950s, the first AP was synthesized (known as chlorpromazine (CPZ)). This drug has revolutionized the treatment of psychotic disorders. This drug, in addition to the antipsychotic effect, caused severe adverse drug reactions in patients, in particular from the neurological system, such as AP-induced extrapyramidal syndrome (EPS) — chlorpromazine-in-duced parkinsonism (CPZ-IP). CPZ-IP characterized by the occurrence of motor disorders. CPZ-IP is as a result of damage to the basal ganglia and subcortical-thalamic connections. Drug-induced EPS is subdivided into primary and secondary. Among the primary EPS, drug-IP is the most common (the leading form of secondary parkinsonism). Pharmacogenetic markers of CPZ safety are being actively studied. Some pharmacogenetic markers of therapy safety have been established: single nucleotide variants/polymorphisms of candidate genes for dopaminergic receptors D2 and D3 (DRD2 (rs1799732 (-141C Ins/Del)), DRD3 (rs6280 (Ser9Gly)), laforine phosphatase (EPM2A (rs1415744 (C/T)).
About the Authors
E. E. VaimanRussian Federation
Elena E. Vaiman
192019, St.Petersburg, Russian Federation; tel.: +79644331333
M. A. Novitsky
Russian Federation
Maxim A. Novitsky
192019, St.Petersburg, Russian Federation
R. F. Nasyrova
Russian Federation
Regina F. Nasyrova
192019, St.Petersburg, Russian Federation; tel.: +7(812)6700220 7813
References
1. Lehmann, H.E., Hanrahan, G.E. Chlorpromazine: New inhibiting agent for psychomotor excitement and manic states. Archives of Neurology and Psychiatry 1954, 71, 227-237. doi:10.1001/archneurpsyc.1954.023203800
2. Shorter, E. A History of Psychiatry. In: From the Era of Asylum to the Age of Prozac. New York: John Wiley & Sons, Inc. 1997
3. Lopez-Munoz, F., Alamo, C., Cuenca, E., Shen, W., Clervoy, P., Rubio, G. History of the Discovery and Clinical Introduction of chlorpromazine. Annats of Clinical Psychiatry 2005, 17(3), 113-135. doi:10.1080/10401230591002002
4. Mosolov, C.H. Modern antipsychotic pharmacotherapy for schizophrenia. Russian medical journal 2004, 12(10), 646-652. (In Russ)]
5. Rees, L. Chlorpromazine and allied phenotihazine derivatives. Ban Medical Journal Drug Treatment of Disease 1960, 522-525. doi:10.1136/bmj.2.5197.522
6. Adams, C.E., Awad, G.A., Rathbone, J., Thornley, B., Soares-Weiser, K. Chlorpromazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2014; doi:10.1002/14651858.cd000284.pub3
7. Ayd, F. J. Survey of Drug-Induced Extrapyramidal Reactions. JAMA 1961, 175, 1054-1060
8. Rifkin A. Extrapyramidal side effects: a historical perspective // The Journal of Clinical Psychiatry.1987; 48(1): 3-6. PMID 2887555
9. Mi, H., Thomas, P.D., Ring, H.Z., Jiang, R., Sangkuhl, K., Klein, T.E., Altman, R.B. PharmGKB summary. Pharmacogenetics and Genomics 2011, 21(6), 350-356. doi:10.1097/FPC.0b013e32833ee605
10. Meites, J. Clemens, J.A. Hypothalamic control of prolactin secretion. Vitamins and Hormones 1972, 165-221. doi:10.1016/s0083-6729(08)60796-7
11. Gokhale, S., Gulati, O., Parikh, H. An investigation of the adrenergic blocking action of chlorpromazine. British Journal of Pharmacology and Chemotherapy 1964, 23(3), 508-520. doi:10.1111/j.1476-5381.1964.tb01606.x
12. Carlsson, A., Lindqvist, M. Effect of chlorpromazine or haloperidol on formation of 3- methoxytyramine and nor-metanephrine in mouse brain. Acta Pharmacologica et Toxicologica 1963, 20(2), 140-144. doi:10.1111/j.1600-0773.1963.tb01730.x
13. Anden, N., Roos, B., Werdinius, B. Effects of chlorpromazine, haloperidol, and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sciences 1964, 3(2), 149-158. doi:10.1016/0024-3205(64)90196-1
14. Prada, M., Pletscher, A. Acceleration of cerebral dopamine turnover by chlorpromazine. Experientia 1966, 22(7), 465-466. doi:10.1007/bf01900988
15. Gey, K.F., Pletscher, A. Acceleration of turnover of 14C-catecholamines in rat brain by chlorpromazine. Experientia 1968, 24, 335-336. doi:10.1007/bf02140804
16. Nyback, H., Sedvall, G. Effect of chlorpromazine on accumulation and disappearance of catecholamines formed from ty-rosine-C14 in brain. Journal of Pharmacology and Experimental Therapeutics 1968, 162, 294-301.PMID 5666984
17. Seeman, P., Lee, T., Chau-Wong, M., Wong, K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976, 261, 717-719. doi:10.1038/261717a0
18. Courvoisier, S., Fournal, J., Ducrot, R., Kolsky, Koetchet P. Proprietes pharmacodynamiques du chlorhydrate de chloro-3 (dimethylamino-3' propyl) - 10 phenothiazine (4.560 R.P.). Archive of International Pharmacodynamics 1953, 92, 305-361
19. Mailman, R., Murthy, V. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Current Pharmaceutical Design 2010, 16(5), 488- 501. doi:10.2174/138161210790361461
20. Mashkovsky M. D. Medicines. - 16th edition. - M .: Novaya Volna, 2005 .-- S. 52, 763 .-- 1200 p. (In Russ.)
21. Dahl, S.G., Strandjord, R.E. Pharmacokinetics of chlorpromazine after single and chronic dosage. Clinical Pharmacology & Therapeutics 1977, 21(4), 437-448. doi:10.1002/cpt1977214437
22. Usdin, E. The assay of ehlorpromazine and metabolites in blood, urine, and other tissues. CRC Critical Reviews in Clinical Laboratory Sciences 1971, 2(3), 347- 391. doi:10.3109/10408367109151312
23. Yeung, P.K.F., Hubbard, J.W., Korchinski, E.D., Midha, K.K. Pharmacokinetics of chlorpromazine and key metabolites. European Journal of Clinical Pharmacology 1993, 45(6), 563-569. doi:10.1007/bf00315316
24. Mackay, A.V.P., Healey, A.F., Baker, J. The relationship of plasma chlorpromazine to its 7-hydroxy and sulphoxide metabolites in a large population of ehroniesehizophrenics. British Journal of Clinical Pharmacology 1974, 1(5), 425-430. doi:10.1111/j.1365-2125.1974.tb00281.x
25. Davidson, J.D., Terry, L.L., Sjoerdsma, A. Action and metabolism of chlorpromazine sulfoxide in man. The Journal of Pharmacology and Experimental Therapeutics 1957, 121(1), 8-12. PMID 13481822
26. Sakalis, G., Curry, S.H., Mould, G.P., Lader, M.H. Physiologie and clinieal effeets of chlorpromazine and their relationship to plasma level. Clinical Pharmacology & Therapeutics 1972, 13(6), 931-946. doi:10.1002/cpt1972136931
27. Dahl, S.G., Strandjord, R.E. Pharmacokinetics of chlorpromazine after single and chronic dosage. Clinical Pharmacology & Therapeutics 1977, 21(4), 437-448. doi:10.1002/cpt1977214437
28. Hill, M.J., Reynolds, G.P. 5-HT2C receptor gene polymorphisms associated with antipsychotic drug actionalterpromoterac-tivity. Brain Research 2007, 1149, 14-17. doi:10.1016/j.brainres.2007.02.038
29. Hollister, L.E., Curry, S.H. Urinary exeretion of ehlorpromazine metabolites following single doses and in steady-state conditions. Research Communications in Chemical Pathology and Pharmacology 1971, 2(3), 330- 338. PMID 4948435
30. Gibaldi, M., Feldman, S. Route of administration and drug metabolism. European Journal of Pharmacology 1972, 19(3), 323329. doi:10.1016/0014-2999(72)90098-2
31. Yoshii, K., Kobayashi, K., Tsumuji, M., Tani, M., Shimada, N., Chiba, K. Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sciences 2000, 67(2), 175-184. doi:10.1016/s0024-3205(00)00613-5
32. Curry, S.H. Chlorpromazine: Concentrations in Plasma, Excretion in Urine and Duration of Effect. Proc R Soc Med 1971, 64(3), 285-289. PMID 5551485
33. Jaworski, T.J., Hawes, E.M., McKay, G., Midha, K.K. The Metabolism of chlorpromazine N-Oxide in the Rat. Xenobiotica 1988, 18(12), 1439- 1447. doi:10.3109/00498258809042266
34. Clinical psychopharmacogenetics, ed. Nasyrova, R.F., Neznanov, N.G.. - SPb: DEAN Publishing House, 2019. — 405 p. (In Russ.)
35. Arinami, T. A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Human Molecular Genetics 1997, 6(4), 577-582. doi:10.1093/hmg/6.4.577
36. Ray, W.A., Meredith, S., Thapa, P.B., Meador, K.G., Hall, K., Murray, K.T. Antipsychotics and the risk of sudden cardiac death. Archives General Psychiatry 2001, 58(12), 1161- 1167. doi:10.1001/archpsyc.58.12.116
37. Wu, S., Xing, Q., Gao, R., Li, X., Gu, N., Feng, G., He, L. Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neuroscience Letters 2005, 376(1), 1-4. doi:10.1016/j.neulet.2004.11.014
38. Jonsson, E.G., Nothen, M.M., Grunhage, F., Farde, L., Nakashima, Y., Propping, P., Sedvall, G.C. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Molecular Psychiatry 1999, 4(3), 290-296. doi:10.1038/sj.mp.4000532
39. Mihara, K., Kondo, T., Suzuki, A., Yasui, N., Ono, S., Otani, K., Kaneko, S. No relationship between -141C Ins/ Del polymorphism in the promoter region of dopamine D2 receptor and extrapyramidal adverse effects of selective dopamine D2 antagonists in schizophrenic patients: a preliminary study. Psychiatry Research 2001, 101(1), 33- 38. doi:10.1016/s0165-1781(00)00247-x
40. Reynolds, G.P., Yao, Z., Zhang, X., Sun, J., Zhang, Z. Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. European Neuropsychopharmacology 2005, 15(2), 143-151. doi:10.1016/j.euroneuro.2004.07.001
41. Andrade D.M., Turnbull J., Minassian B.A.Lafora disease, seizures and sugars // Acta Myol. 2007; 26: 83-86. PMID: 17915579
42. Porcelli, S., Balzarro, B., Lee, S.-J., Han, C., Patkar, A.A., Pae, C.U., Serretti, A. PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study. Neuropsychobiology 2016, 73(3), 160-168. doi:10.1159/000445295
Review
For citations:
Vaiman E.E., Novitsky M.A., Nasyrova R.F. Pharmacogenetics of chlorpromazine and its role in the development of antipsychotic-induced parkinsonism. Personalized Psychiatry and Neurology. 2021;1(1):11-17. https://doi.org/10.52667/2712-9179-2021-1-1-11-17