Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment

European Neuropsychopharmacology

Volumn 23, Issue 11, 2013, Pages 1636-1644

  Karlsson, Louise ^a   Carlsson, Björn ^a   Hiemke, Christoph ^b   Ahlner, Johan ^a,c   Bengtsson, Finn ^a   Schmitt, Ulrich ^b   Kugelberg, Fredrik C ^a,c  

^a LINKÖPING UNIVERSITY   (Sweden)

^b UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^c DEPARTMENT OF FORENSIC GENETICS AND FORENSIC TOXICOLOGY   (Sweden)

Author keywords

Abcb1ab; Citalopram; Enantiomers; Escitalopram; Knockout mice; P glycoprotein

Indexed keywords

CITALOPRAM; ESCITALOPRAM; MULTIDRUG RESISTANCE PROTEIN;

ACUTE DRUG ADMINISTRATION; ANIMAL EXPERIMENT; ARTICLE; CHRONIC DRUG ADMINISTRATION; CONTROLLED STUDY; DRUG BRAIN LEVEL; ENANTIOMER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; KNOCKOUT MOUSE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEFICIENCY; SINGLE DRUG DOSE; STEREOCHEMISTRY; TREATMENT DURATION;

ABCB1AB; CITALOPRAM; ENANTIOMERS; ESCITALOPRAM; KNOCKOUT MICE; P-GLYCOPROTEIN;

ANIMALS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; BRAIN; CITALOPRAM; MALE; MICE; MICE, KNOCKOUT; P-GLYCOPROTEIN;

EID: 84886783723     PISSN: 0924977X     EISSN: 18737862     Source Type: Journal    
DOI: 10.1016/j.euroneuro.2013.01.003     Document Type: Article

References (61)

1. Bachmeier C.J., Beaulieu-Abdelahad D., Ganey N.J., Mullan M.J., Levin G.M. Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm. Drug Dispos. 2011, 32:233-244.
2. Bourin M., Colombel M.C., Redrobe J.P., Nizard J., Hascoet M., Baker G.B. Evaluation of efficacies of different classes of antidepressants in the forced swimming test in mice at different ages. Prog. Neuropsychopharmacol. Biol. Psychiatry 1998, 22:343-351.
3. Brøsen K., Naranjo C.A. Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram. Eur. Neuropsychopharmacol. 2001, 11:275-283.
4. Bundgaard C., Jes Nyberg Jensen C., Garmer M. Species comparison of in vivo P-glycoprotein mediated brain efflux using mdr1a deficient rats and mice. Drug Metab. Dispos. 2012, 40:461-466.
5. Burke W.J., Gergel I., Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J. Clin. Psychiatry 2002, 63:331-336.
6. Carlsson B., Olsson G., Reis M., Walinder J., Nordin C., Lundmark J., Scordo M.G., Dahl M.L., Bengtsson F., Ahlner J. Enantioselective analysis of citalopram and metabolites in adolescents. Ther. Drug Monit. 2001, 23:658-664.
7. Choong E., Dobrinas M., Carrupt P.A., Eap C.B. The permeability P-glycoprotein: a focus on enantioselectivity and brain distribution. Expert Opin. Drug Metab. Toxicol. 2010, 6:953-965.
8. Cordon-Cardo C., O'Brien J.P., Casals D., Rittman-Grauer L., Biedler J.L., Melamed M.R., Bertino J.R. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Natl. Acad. Sci. USA 1989, 86:695-698.
9. Crowley J.J., Blendy J.A., Lucki I. Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test. Psychopharmacology (Berl) 2005, 183:257-264.
10. Cryan J.F., O'Leary O.F., Jin S.H., Friedland J.C., Ouyang M., Hirsch B.R., Page M.E., Dalvi A., Thomas S.A., Lucki I. Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors. Proc. Natl. Acad. Sci. USA 2004, 101:8186-8191.
11. Devault A., Gros P. Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities. Mol. Cell Biol. 1990, 10:1652-1663.
12. Doran A., Obach R.S., Smith B.J., Hosea N.A., Becker S., Callegari E., Chen C., Chen X., Choo E., Cianfrogna J., Cox L.M., Gibbs J.P., Gibbs M.A., Hatch H., Hop C.E., Kasman I.N., Laperle J., Liu J., Liu X., Logman M., Maclin D., Nedza F.M., Nelson F., Olson E., Rahematpura S., Raunig D., Rogers S., Schmidt K., Spracklin D.K., Szewc M., Troutman M., Tseng E., Tu M., Van Deusen J.W., Venkatakrishnan K., Walens G., Wang E.Q., Wong D., Yasgar A.S., Zhang C. The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model. Drug Metab. Dispos. 2005, 33:165-174.
13. Ebinger M., Uhr M. ABC drug transporter at the blood-brain barrier: effects on drug metabolism and drug response. Eur. Arch. Psychiatry Clin. Neurosci. 2006, 256:294-298.
14. Ehret M.J., Levin G.M., Narasimhan M., Rathinavelu A. Venlafaxine induces P-glycoprotein in human Caco-2 cells. Hum. Psychopharmacol. 2007, 22:49-53.
15. Ejsing T.B., Morling N., Linnet K. A review on the relation between the brain-serum concentration ratio of drugs and the influence of P-glycoprotein. Drug Metabol. Drug Interact. 2007, 22:113-129.
16. Endres C.J., Hsiao P., Chung F.S., Unadkat J.D. The role of transporters in drug interactions. Eur. J. Pharm. Sci. 2006, 27:501-517.
17. Fudio S., Borobia A.M., Piñana E., Ramírez E., Tabarés B., Guerra P., Carcas A., Frías J. Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram. Eur. J. Pharmacol. 2010, 626:200-204.
18. Garrigues A., Loiseau N., Delaforge M., Ferté J., Garrigos M., André F., Orlowski S. Characterization of two pharmacophores on the multidrug transporter P-glycoprotein. Mol. Pharmacol. 2002, 62:1288-1298.
19. Gutmann H., Poller B., Buter K.B., Pfrunder A., Schaffner W., Drewe J. Hypericum perforatum: which constituents may induce intestinal MDR1 and CYP3A4 mRNA expression?. Planta Med. 2006, 72:685-690.
20. Hoffmeyer S., Burk O., von Richter O., Arnold H.P., Brockmoller J., Johne A., Cascorbi I., Gerloff T., Roots I., Eichelbaum M., Brinkmann U. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. USA 2000, 97:3473-3478.
21. Hyttel J., Bogeso K.P., Perregaard J., Sanchez C. The pharmacological effect of citalopram resides in the (S)-(+)-enantiomer. J. Neural Transm. Gen. Sect. 1992, 88:157-160.
22. Karlsson L., Hiemke C., Carlsson B., Josefsson M., Ahlner J., Bengtsson F., Schmitt U., Kugelberg F.C. Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model. Psychopharmacology (Berl) 2011, 215:367-377.
23. Karlsson L., Schmitt U., Josefsson M., Carlsson B., Ahlner J., Bengtsson F., Kugelberg F.C., Hiemke C. Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein. Eur. Neuropsychopharmacol. 2010, 20:632-640.
24. Kim R.B., Leake B.F., Choo E.F., Dresser G.K., Kubba S.V., Schwarz U.I., Taylor A., Xie H.G., McKinsey J., Zhou S., Lan L.B., Schuetz J.D., Schuetz E.G., Wilkinson G.R. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther. 2001, 70:189-199.
25. Kirschbaum K.M., Henken S., Hiemke C., Schmitt U. Pharmacodynamic consequences of P-glycoprotein-dependent pharmacokinetics of risperidone and haloperidol in mice. Behav. Brain Res. 2008, 188:298-303.
26. Kosel M., Amey M., Aubert A.C., Baumann P. In vitro metabolism of citalopram by monoamine oxidase B in human blood. Eur. Neuropsychopharmacol. 2001, 11:75-78.
27. Kugelberg F.C., Apelqvist G., Carlsson B., Ahlner J., Bengtsson F. In vivo steady-state pharmacokinetic outcome following clinical and toxic doses of racemic citalopram to rats. Br. J. Pharmacol. 2001, 132:1683-1690.
28. Kugelberg F.C., Carlsson B., Ahlner J., Bengtsson F. Stereoselective single-dose kinetics of citalopram and its metabolites in rats. Chirality 2003, 15:622-629.
29. Lepola U., Wade A., Andersen H.F. Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of two positive placebo-controlled studies in major depressive disorder. Int. Clin. Psychopharmacol. 2004, 19:149-155.
30. Linnet K., Ejsing T.B. A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur. Neuropsychopharmacol. 2008, 18:157-169.
31. Loscher W., Potschka H. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog. Neurobiol. 2005, 76:22-76.
32. Mansari M.E., Wiborg O., Mnie-Filali O., Benturquia N., Sanchez C., Haddjeri N. Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies. Int. J. Neuropsychopharmacol. 2007, 10:31-40.
33. Mayer U., Wagenaar E., Dorobek B., Beijnen J.H., Borst P., Schinkel A.H. Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833. J. Clin. Invest. 1997, 100:2430-2436.
34. Mnie-Filali O., Faure C., Mansari M.E., Lambas-Senas L., Berod A., Zimmer L., Sanchez C., Haddjeri N. R-citalopram prevents the neuronal adaptive changes induced by escitalopram. Neuroreport 2007, 18:1553-1556.
35. Montgomery S.A., Loft H., Sanchez C., Reines E.H., Papp M. Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol. Toxicol. 2001, 88:282-286.
36. Mork A., Kreilgaard M., Sanchez C. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats. Neuropharmacology 2003, 45:167-173.
37. Narang V.S., Fraga C., Kumar N., Shen J., Throm S., Stewart C.F., Waters C.M. Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier. Am. J. Physiol. Cell Physiol. 2008, 295:C440-450.
38. O'Brien F.E., Dinan T.G., Griffin B.T., Cryan J.F. Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings. Br. J. Pharmacol. 2012, 165:289-312.
39. Olesen O.V., Linnet K. Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes. Pharmacology 1999, 59:298-309.
40. Owens M.J., Knight D.L., Nemeroff C.B. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol. Psychiatry 2001, 50:345-350.
41. Perloff M.D., von Moltke L.L., Greenblatt D.J. Ritonavir and dexamethasone induce expression of CYP3A and P-glycoprotein in rats. Xenobiotica 2004, 34:133-150.
42. Reis M., Lundmark J., Bengtsson F. Therapeutic drug monitoring of racemic citalopram: a 5-year experience in Sweden, 1992-1997. Ther. Drug Monit. 2003, 25:183-191.
43. Rochat B., Amey M., Baumann P. Analysis of enantiomers of citalopram and its demethylated metabolites in plasma of depressive patients using chiral reverse-phase liquid chromatography. Ther. Drug Monit. 1995, 17:273-279.
44. Rochat B., Baumann P., Audus K.L. Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium. Brain Res. 1999, 831:229-236.
45. 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. 1998, 56:15-23.
46. Sanchez C., Bergqvist P.B.F., Brennum L.T., Gupta S., Hogg S., Larsen A., Wiborg O. Escitalopram, the S-(+)-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities. Psychopharmacology (Berl) 2003, 167:353-362.
47. Sanchez C., Bogeso K.P., Ebert B., Reines E.H., Braestrup C. Escitalopram versus citalopram: the surprising role of the R-enantiomer. Psychopharmacology (Berl) 2004, 174:163-176.
48. Sanchez C., Gruca P., Bien E., Papp M. R-citalopram counteracts the effect of escitalopram in a rat conditioned fear stress model of anxiety. Pharmacol. Biochem. Behav. 2003, 75:903-907.
49. Sanchez C., Gruca P., Papp M. R-citalopram counteracts the antidepressant-like effect of escitalopram in a rat chronic mild stress model. Behav. Pharmacol. 2003, 14:465-470.
50. Sanchez C., Kreilgaard M. R-citalopram inhibits functional and 5-HTP-evoked behavioural responses to the SSRI, escitalopram. Pharmacol. Biochem. Behav. 2004, 77:391-398.
51. Thiebaut F., Tsuruo T., Hamada H., Gottesman M.M., Pastan I., Willingham M.C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA 1987, 84:7735-7738.
52. Thiebaut F., Tsuruo T., Hamada H., Gottesman M.M., Pastan I., Willingham M.C. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J. Histochem. Cytochem. 1989, 37:159-164.
53. Uhr M., Grauer M.T. abcb1ab P-glycoprotein is involved in the uptake of citalopram and trimipramine into the brain of mice. J. Psychiatr. Res. 2003, 37:179-185.
54. Uhr M., Grauer M.T., Holsboer F. Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. Biol. Psychiatry 2003, 54:840-846.
55. Uhr M., Grauer M.T., Yassouridis A., Ebinger M. Blood-brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls. J. Psychiatr. Res. 2007, 41:179-188.
56. Uhr M., Steckler T., Yassouridis A., Holsboer F. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology 2000, 22:380-387.
57. Uhr M., Tontsch A., Namendorf C., Ripke S., Lucae S., Ising M., Dose T., Ebinger M., Rosenhagen M., Kohli M., Kloiber S., Salyakina D., Bettecken T., Specht M., Putz B., Binder E.B., Muller-Myhsok B., Holsboer F. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron 2008, 57:203-209.
58. Wade A., Michael Lemming O., Bang Hedegaard K. Escitalopram 10mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int. Clin. Psychopharmacol. 2002, 17:95-102.
59. Wang J.S., Ruan Y., Taylor R.M., Donovan J.L., Markowitz J.S., DeVane C.L. The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein. Int. J. Neuropsychopharmacol. 2004, 7:415-419.
60. Wikell C., Apelqvist G., Carlsson B., Hjorth S., Bergqvist P.B.F., Kugelberg F.C., Ahlner J., Bengtsson F. Pharmacokinetic and pharmacodynamic responses to chronic administration of the selective serotonin reuptake inhibitor citalopram in rats. Clin. Neuropharmacol. 1999, 22:327-336.
61. Yin O.Q., Wing Y.K., Cheung Y., Wang Z.J., Lam S.L., Chiu H.F., Chow M.S. Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients. J. Clin. Psychopharmacol. 2006, 26:367-372.