Enantiomers' potential in psychopharmacology - A critical analysis with special emphasis on the antidepressant escitalopram

European Neuropsychopharmacology

Volumn 12, Issue 5, 2002, Pages 433-444

  Baumann, Pierre ^a   Zullino, Daniele F ^a   Eap, Chin B ^a  

^a DEPT UNIV DE PSYCHIATRIE ADULTE   (Switzerland)

Author keywords

Antidepressant; Citalopram; Depression; Enantiomer; Escitalopram; SSRI

Indexed keywords

2 HYDROXYNORTRIMIPRAMINE; 2 HYDROXYTRIMIPRAMINE; CITALOPRAM; DEBRISOQUINE; DINORCITALOPRAM; DRUG METABOLITE; ESCITALOPRAM; FLUOXETINE; FLUVOXAMINE; MESORIDAZINE; METHADONE; MIANSERIN; MILNACIPRAN; MIRTAZAPINE; NORCITALOPRAM; NORFLUOXETINE; NORTRIMIPRAMINE; PAROXETINE; PSYCHOTROPIC AGENT; REBOXETINE; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; SULFORIDAZINE; THIORIDAZINE; THIORIDAZINE 2,5 DISULFOXIDE; THIORIDAZINE SULFOXIDE; TRICYCLIC ANTIDEPRESSANT AGENT; TRIMIPRAMINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VENLAFAXINE;

AREA UNDER THE CURVE; ARTICLE; BINDING ASSAY; CHIRALITY; CLINICAL TRIAL; DEPRESSION; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENANTIOMER; HUMAN; NONHUMAN; ORTHOSTATIC HYPOTENSION; PHARMACOGENETICS; PRIORITY JOURNAL; PSYCHOPHARMACOLOGY; RACEMIC MIXTURE; RATING SCALE; RISK BENEFIT ANALYSIS; SIDE EFFECT; STEREOCHEMISTRY; STEREOISOMERISM; STRUCTURE ANALYSIS; TREATMENT OUTCOME;

ANIMALS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; CITALOPRAM; DEPRESSION; FLUOXETINE; HUMANS; MENTAL DISORDERS; MIANSERIN; MOLECULAR STRUCTURE; PSYCHOTROPIC DRUGS; SEROTONIN UPTAKE INHIBITORS; STEREOISOMERISM; THIORIDAZINE; TRIMIPRAMINE;

EID: 0036787115     PISSN: 0924977X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0924-977X(02)00051-2     Document Type: Article

References (78)

1. Agranat I., Caner H. Intellectual property and chirality of drugs. Drug Discov. Today. 4:1999;313-321.
2. Baker G.B., Coutts R.T., Holt A. Metabolism and chirality in psychopharmacology. Biol. Psychiatry. 36:1994;211-213.
3. Baumann P. Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin. Pharmacokinet. 31:1996;444-469.
4. Baumann P., Eap C.B. Pharmacogenetics. Lerer B., Pharmacological, Pharmacokinetic and Clinical Aspects of chiral psychotropic drugs. 2002;Cambridge University Press, Cambridge. in press.
5. Baumann, P., Eap, C.B., 2002b. Pharmacogenetics of chiral psychotropic drugs. In: Lerer, B. (Ed.), Pharmacogenetics of Psychotropic Drugs. Cambridge University Press, Cambridge, in press.
6. Bergqvist, P.B., Brennum, L.T., Sánchez, C., 2001. Escitalopram mediates citalopram's inhibition of dorsal raphe nucleus (DRN) 5HT neural activity. In: New Research Program and Abstracts of the 154th Annual Meeting of the American Psychiatric Association; 5-10 May, 2001, New Orleans, LA. Abstract NR557.
7. Bezchlibnyk-Butler K., Aleksic I., Kennedy S.H. Citalopram - a review of pharmacological and clinical effects. J. Psychiatry Neurosci. 25:2000;241-254.
8. Bondolfi G., Chautems C., Rochat B., Bertschy G., Baumann P. Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of fluvoxamine augmentation. Psychopharmacology. 128:1996;421-425.
9. Bondolfi G., Lissner C., Kosel M., Eap C.B., Baumann P. Fluoxetine augmentation in citalopram non-responders: pharmacokinetic and clinical consequences. Int. J. Neuropsychopharmacol. 3:2000;55-60.
10. Burke, W.J., Gergel, I., Bose Anjana, 2002. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J. Clin Psychiatry 63, 4.
11. Caldwell J. Do single enantiomers have something special to offer? Hum. Psychopharmacol. Clin. Exp. 16:(Suppl. 2):2001;S67-S72.
12. Dahl M.-L., Tybring G., Elwin C.-E., Alm C., Andreasson K., Gyllenpalm M., Bertilsson L. Stereoselective disposition of mianserin is related to debrisoquine hydroxylation polymorphism. Clin. Pharmacol. Ther. 56:1994;176-183.
13. ®) enhances noradrenergic and serotonergic transmission. Hum. Psychopharmacol. Clin. Exp. 10:(Suppl. 2):1995;107-118.
14. Drayer D.E. 1993. The early history of stereochemistry. Wainer I.W., Drug Stereochemistry: Analytical Methods and Pharmacology. 2nd Edition. Marcel Dekker, New York. 1-24.
15. Dyer K.R., White J.M., Foster D.J.R., Bochner F., Menelaou A., Somogyi A.A. The relationship between mood state and plasma methadone concentration in maintenance patients. J. Clin. Psychopharmacol. 21:2001;78-84.
16. Eap C.B., Bourquin M., Martin J.-L., Spagnoli J., Livoti S., Powell K., Baumann P., Déglon J.-J. Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment. Drug Alcohol Depend. 61:2000;47-54.
17. Eap C.B., Bender S., Gastpar M., Fischer W., Haarmann C., Powell K., Jonzier-Perey M., Cochard N., Baumann P. Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients. Ther. Drug Monit. 22:2000;209-214.
18. Eap C.B., Broly F., Mino A., Hämmig R., Deglon J.J., Uehlinger C., Meili D., Chevalley G., Bertschy A.F., Zullino D., Kosel M., Preisig M., Baumann P. Cytochrome P450 2D6 genotype and methadone steady-state concentrations. J. Clin. Psychopharmacol. 21:2001;229-234.
19. Eap C.B., Cuendet C., Baumann P. Binding of d-methadone, l-methadone, and dl-methadone to proteins in plasma of healthy volunteers: role of the variants of alpha1-acid glycoprotein. Clin. Pharmacol. Ther. 47:1990;338-346.
20. Eap C.B., Déglon J.-J., Baumann P. Pharmacokinetics and pharmacogenetics of methadone: clinical relevance. Heroin Add. Rel. Clin. Probl. 1:1999;19-34.
21. Eap C.B., Lima C.A., Macciardi F., Woggon B., Powell K., Baumann P. Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine. Ther. Drug Monit. 20:1998;7-13.
22. Fjordside L.J., Jeppesen U., Eap C.B., Powell K., Baumann P., Brøsen K. The stereo-selective metabolism of fluoxetine in poor and extensive metabolizers of sparteine. Pharmacogenetics. 9:1999;55-60.
23. Foglia J.P., Pollock B.G., Kirshner M.A., Rosen J., Sweet R., Mulsant B. Psychopharmacology in geriatric populations - plasma levels of citalopram enantiomers and metabolites in elderly patients. Psychopharmacol. Bull. 33:1997;109-112.
24. Foster J.R., Somogyi A.A., Dyer K.R., White J.M., Bochner F. Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients. Br. J. Clin. Pharmacol. 50:2000;427-440.
25. Gorman J.M., Korotzer A., Su G. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. CNS Spectrums-Academic Supplement. Int. J. Neuropsychiatric Medicine. 7:(suppl. 1):2002;40-44.
26. Hand T.H., Marek G.J., Seiden L.S. Comparison of the effects of mianserin and its enantiomers and metabolites on a behavioural screen for antidepressant activity. Psychopharmacology. 105:1991;453-458.
27. Hartigan-Go K., Bateman D.N., Nyberg G., Martensson E., Thomas S.H.L. Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans. Clin. Pharmacol. Ther. 60:1996;543-553.
28. Hilborn J.W., Lu Z.H., Jurgens A.R., Fang Q.K., Byers P., Wald S.A., Senanayake C.H. A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine. Tetrahedron Lett. 42:2001;8919-8921.
29. Hogg, S., Sánchez, C., 1999. The antidepressant effects of citalopram are mediated by the S-(+)- and not the R-(-)-enantiomer. Eur. Neuropsychopharmacol. 9(Suppl. 1) P.03.137.
30. Hyttel J., Bøgesø K.P., Perregaard J., Sánchez C. The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J. Neural Transm. Gen. Sect. 88:1992;157-160.
31. Kelder J., Funke C., De Boer T., Delbressine L., Leysen D., Nickolson V. A comparison of the physicochemical and biological properties of mirtazapine and mianserin. J. Pharm. Pharmacol. 49:1997;403-411.
32. Keller M.B. Citalopram therapy for depression: a review of 10 years of European experience and data from US clinical trials. J. Clin. Psychiatry. 61:2000;896-908.
33. Kobayashi K., Chiba K., Yagi T., Shimada N., Taniguchi T., Horie T., Tani M., Yamamoto T., Ishizaki T., Kuroiwa Y. Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. J. Pharmacol. Exp. Ther. 280:1997;927-933.
34. Kosel M., Amey M., Aubert A.-C., Baumann P. In vitro metabolism of citalopram by monoamine oxidase B in human blood. Eur. Neuropsychopharmacol. 11:2001;75-78.
35. Kosel M., Gnerre C., Voirol P., Amey M., Rochat B., Bouras C., Testa B., Baumann P. In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations. Mol. Psychiatry. 7:2002;181-188.
36. Kott A., Habel E., Nottingham W. Analysis of behavioural patterns in five cohorts of patients retained in methadone maintenance programs. Mount Sinai J. Med. 68:2001;46-54.
37. Lamzin V.S., Dauter Z., Wilson K.S. How nature deals with stereoisomers. Curr. Opin. Struct. Biol. 5:1995;830-836.
38. Lane R.M., Baker G.B. Chirality and drugs used in psychiatry: nice to know or need to know? Cell. Mol. Neurobiol. 19:1999;355-372.
39. Leinonen E., Koponen H.J., Lepola U. Paroxetine increases serum trimipramine concentration - a report of two cases. Hum. Psychopharmacol. Clin. Exp. 10:1995;345-357.
40. Lepola, U.M., Loft, H., Reines, E.H., 2001. Escitalopram: efficacious and well tolerated in depression management in primary care. In: New Research Program and Abstracts of the 154th Annual Meeting of the American Psychiatric Association; 5-10 May, 2001; New Orleans, LA. Abstract NR431.
41. McClellan K.J., Faulds D. Ropivacaine: an update of its use in regional anaesthesia. Drugs. 60:2000;1065-1093.
42. Meyer J.W., Woggon B., Baumann P., Meyer U.A. Clinical implications of slow sulphoxidation of thioridazine in a poor metaboliser of the debrisoquine type. Eur. J. Clin. Pharmacol. 39:1990;613-614.
43. Miles W.H., Fialcowitz E.J., Halstead E.S. Enantioselective synthesis of (S)- and (R)-fluoxetine hydrochloride. Tetrahedron. 57:2001;9925-9929.
44. Mitchell, P.J., Hogg, S., 2001. Behavioral effects of escitalopram predict rapid antidepressant activity. In: New Research Program and Abstracts of the 154th Annual Meeting of the American Psychiatric Association; 5-10 May, 2001; New Orleans, LA. Abstract NR503.
45. 1A receptor antagonist, WAY-100635. Behav. Pharmacol. 8:1997;585-606.
46. Montgomery S.A., Loft H., Sánchez C., Reines E.H., Papp M. Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol. Toxicol. 88:2001;282-286.
47. Noctor T.A.G., 1993. Enantioselective binding of drugs to plasma proteins. Wainer I.W., Drug Stereochemistry: Analytical Methods and Pharmacology. 2nd Edition. Marcel Dekker, New York, pp. 337-364.
48. Ott R.J., Giacomini K.M., 1993. Stereoselective transport of drugs across epithelia. Wainer I.W., Drug Stereochemistry: Analytical Methods and Pharmacology. 2nd Edition. Marcel Dekker, New York, pp. 281-314.
49. Owens M.J., Knight D.L., Nemeroff C.B. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol. Psychiatry. 50:2001;345-350.
50. Pinder R.M., Van Delft A.M. The potential therapeutic role of the enantiomers and metabolites of mianserin. Br. J. Clin. Pharmacol. 15:(Suppl. 2):1983;269S-276S.
51. Pollock B.A. Citalopram: a comprehensive review. Exp. Opin. Pharmacother. 2:2001;681-698.
52. Ring B.J., Eckstein J.A., Gillespie J.S., Binkley S.N., Van den Branden M., Wrighton S.A. Identification of the human cytochromes p450 responsible for in vitro formation of R- and S-norfluoxetine. J. Pharmacol. Exp. Ther. 297:2001;1044-1050.
53. Robertson D.W., Krushinski J.H., Bymaster F.P., Reid L.R., Wong D.T. Seproxetine: absolute configurations and stereospecific interactions of the enantiomers of norfluoxetine with the serotonin uptake carrier. Pharmacologist. 33:1991;219.
54. Rochat B., Amey M., Gillet M., Meyer U.A., Baumann P. Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics. 7:1997;1-10.
55. Rochat B., Kosel M., Boss G., Testa B., Gillet M., Baumann P. Stereoselective biotransformation of the selective serotonin reuptake inhibitor, citalopram, and its demethylated metabolites by monoamine oxidases in human liver. Biochem. Pharmacol. 56:1998;15-23.
56. Sánchez, C., 2001. Escitalopram: potent anxiolytic effects in rodent models of anxiety. In: New Research Program and Abstracts of the 154th Annual Meeting of the American Psychiatric Association; 5-10 May, 2001; New Orleans, LA. Abstract NR559.
57. Seifritz E., Holsboer-Trachsler E., Hemmeter U., Eap C.B., Baumann P. Increased trimipramine plasma levels during fluvoxamine comedication. Eur. Neuropsychopharmacol. 4:1994;15-20.
58. Sidhu J., Priskorn M., Poulsen M., Segonzac A., Grollier G., Larsen F. Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans. Chirality. 9:1997;686-692.
59. Simonyi M., Gal J., Testa B. Signs of the times: the need for a stereochemically informative generic name system. Trends Pharmacol. Sci. 10:1989;349-354.
60. Sindrup S.H., Brøsen K., Hansen M.G., Aaes-Jørgensen T., Overø K.F., Gram L.F. Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther. Drug Monit. 15:1993;11-17.
61. Steinacher L., Vandel P., Zullino D.F., Eap C.B., Brawand-Amey M., Baumann P. Carbamazepine augmentation in depressive patients non responding to citalopram: a pharmacokinetic and clinical pilot study. Eur. Neuropsychopharmacol. 12:2002;255-260.
62. Stevens J.C., Wrighton S.A. Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J. Pharmacol. Exp. Ther. 266:1993;964-971.
63. 2 receptors in rat brain. Neuropharmacology. 27:1988;1117-1124.
64. Testa B. Chiral aspects of drug metabolism. Trends Pharmacol. Sci. 7:1986;60-64.
65. Timmer C.J., Sitsen J.M., Delbressine L.P. Clinical pharmacokinetics of mirtazapine. Clin. Pharmacokinet. 38:2000;461-474.
66. Tucker G.T. Chiral switches. Lancet. 355:2000;1085-1087.
67. Van Regenmortel M.H.V., Muller S. D-Peptides as immunogens and diagnostic reagents. Curr. Opin. Biotechnol. 9:1998;377-382.
68. Voirol P., Rubin C., Bryois C., Kosel M., Buclin T., Baumann P. Pharmacokinetic consequences of a citalopram treatment discontinuation. Ther. Drug Monit. 21:1999;263-266.
69. von Bahr C., Movin G., Nordin C., Liden A., Hammarlund-Udenaes M., Hedberg A., Ring H., Sjoqvist F. Plasma levels of thioridazine and metabolites are influenced by the debrisoquine hydroxylation phenotype. Clin. Pharmacol. Ther. 49:1991;234-240.
70. von Moltke L.L., Greenblatt D.J., Giancarlo G.M., Granda B.W., Harmatz J.S., Shader R.I. Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab. Dispos. 29:2001;1102-1109.
71. von Moltke L.L., Greenblatt D.J., Grassi J.M., Granda B.W., Venkatakrishnan K., Duan S.X., Fogelman S.M., Harmatz J.S., Shader R.I. Citalopram and desmethylcitalopram in vitro: human cytochromes mediating transformation, and cytochrome inhibitory effects. Biol. Psychiatry. 46:1999;839-849.
72. Wade A., Michael Lemming O., Bang Hedegaard K. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int. Clin. Psychopharmacol. 17:2002;95-102.
73. Wainer I.W., Marcotte A.A.M., 1993. Stereochemical terms and concepts. Wainer I.W., Drug Stereochemistry: Analytical Methods and Pharmacology. 2nd Edition. Marcel Dekker, New York, pp. 25-34.
74. White P.F., Ham J., Way W.L., Trevor A.J. Pharmacology of ketamine isomers in surgical patients. Anesthesiology. 52:1980;231-239.
75. Wong D.T., Bymaster F.P., Engleman E.A. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: twenty years since its first publication. Life Sci. 57:1995;411-441.
76. Wong D.T., Bymaster F.P., Reid L.R., Mayle D.A., Krushinski J.H., Robertson D.W. Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology. 8:1993;337-344.
77. Wong D.T., Reid L.R., Threlkeld P.G. Suppression of food intake in rats by fluoxetine: comparison of enantiomers and effects of serotonin antagonists. Pharmacol. Biochem. Behav. 31:1988;475-479.
78. 3 receptors. J. Pharm. Pharmacol. 45:1993;711-714.