Topiramate in the new generation of drugs: efficacy in the treatment of alcoholic patients

Current Pharmaceutical Design

Volumn 16, Issue 19, 2010, Pages 2103-2112

  Johnson, Bankole A ^a   Ait Daoud, Nassima ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Alcohol; Craving; Gamma aminobutyric acid; Glutamate; Impulsivity; Relapse; Topiramate; Treatment

Indexed keywords

ACAMPROSATE; ACETAZOLAMIDE; ALCOHOL; AMITRIPTYLINE; BARBITURIC ACID DERIVATIVE; BENZODIAZEPINE DERIVATIVE; CARBAMAZEPINE; DIGOXIN; DISULFIRAM; HALOPERIDOL; LAMOTRIGINE; LITHIUM; METFORMIN; NALTREXONE; OPIATE DERIVATIVE; ORAL CONTRACEPTIVE AGENT; PHENYTOIN; PLACEBO; PROGESTERONE; RISPERIDONE; TOPIRAMATE; TRAMADOL; VALPROIC ACID; FRUCTOSE; NEUROPROTECTIVE AGENT;

ADD ON THERAPY; ALCOHOL CONSUMPTION; ALCOHOL WITHDRAWAL; ALCOHOLISM; ANOREXIA; ANTICONVULSANT ACTIVITY; ARTICLE; ATTENTION DISTURBANCE; BLOOD LEVEL; CHOLELITHIASIS; CLINICAL TRIAL; CLOSED ANGLE GLAUCOMA; COGNITIVE DEFECT; COMORBIDITY; CONCENTRATION LOSS; CONTROLLED CLINICAL TRIAL; CONVULSION; CRISIS INTERVENTION; DIABETES MELLITUS; DIARRHEA; DIZZINESS; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; EPILEPSY; FATIGUE; FLU LIKE SYNDROME; HUMAN; HYPERTHERMIA; IMPULSE CONTROL DISORDER; INJURY; INSOMNIA; LENNOX GASTAUT SYNDROME; MEMORY DISORDER; METABOLIC ACIDOSIS; MIGRAINE; MYALGIA; MYOPIA; NAUSEA; NEPHROLITHIASIS; NERVOUSNESS; NEUROPROTECTION; NONHUMAN; OBESITY; PARESTHESIA; PATIENT COMPLIANCE; PATIENT SATISFACTION; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; PRURITUS; PSYCHOMOTOR RETARDATION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RELAPSE; SIDE EFFECT; SINUSITIS; SOMNOLENCE; SWEATING; SYNCOPE; TASTE AVERSION; TONIC CLONIC SEIZURE; TREATMENT OUTCOME; WEIGHT REDUCTION; ANALOGS AND DERIVATIVES; ANIMAL; DOSE RESPONSE; DRINKING BEHAVIOR; MULTIMODALITY CANCER THERAPY; PREVENTION AND CONTROL; PROCEDURES; PSYCHOTHERAPY;

ALCOHOL DRINKING; ALCOHOLISM; ANIMALS; COMBINED MODALITY THERAPY; DOSE-RESPONSE RELATIONSHIP, DRUG; FRUCTOSE; HUMANS; NEUROPROTECTIVE AGENTS; PSYCHOTHERAPY, BRIEF;

EID: 77955640603     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161210791516404     Document Type: Article

References (107)

1. Resor SR Jr, Resor LD, Woodbury DM, Kemp JW. Acetazolamide. In: Levy RH, Mattson RH, Meldrum BS, Eds. Antiepileptic drugs. New York: Raven Press 1995; pp. 969-985.
2. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the fourth Eilat conference (EILAT IV). Epilepsy Res 1999; 34: 1-41.
3. Abou-Khalil B. Topiramate in the long-term management of refractory epilepsy. Topiramate YOL Study Group. Epilepsia 2000; 41(suppl 1): S72-6.
4. Montouris GD, Biton V, Rosenfeld WE. Nonfocal generalized tonic-clonic seizures: response during long-term topiramate treatment. Topiramate YTC/YTCE Study Group. Epilepsia 2000; 41(suppl 1): S77-81.
5. Reddy DS. Newer GABAergic agents for pharmacotherapy of infantile spasms. Drugs Today 2002; 38: 657-75.
6. Czuczwar SJ, Patsalos PN. The new generation of GABA enhancers: potential in the treatment of epilepsy. CNS Drugs 2001; 15: 339-50.
7. White HS. Mechanism of action of newer anticonvulsants. J Clin Psychiatry 2003; 64: 5-8.
8. Zupanc ML. Infantile spasms. Expert Opin Pharmacother 2003; 4: 2039-48.
9. Niebauer M, Gruenthal M. Topiramate reduces neuronal injury after experimental status epilepticus. Brain Res 1999; 837: 263-9.
10. Koh S, Jensen FE. Topiramate blocks perinatal hypoxia-induced seizures in rat pups. Ann Neurol 2001; 50: 366-72.
11. Edmonds HL Jr, Jiang YD, Zhang PY, et al. Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration. Life Sci 2001; 69: 2265-77.
12. Angehagen M, Ben-Menachem E, Ronnback L, et al. Topiramate protects against glutamate- and kainate-induced neurotoxicity in primary neuronal-astroglial cultures. Epilepsy Res 2003; 54: 63-71.
13. Khan SH, Wright SL, Banigesh A, et al. Antiischemic effects of topiramate in a transient global forebrain ischemia model: a neurochemical, histological, and behavioral evaluation. Neurochem Res 2003; 28: 1235-9.
14. Qian J, Noebels JL. Topiramate alters excitatory synaptic transmission in mouse hippocampus. Epilepsy Res 2003; 55: 225-33.
15. White HS, Brown SD, Woodhead JH, et al. Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res 1997; 28: 167-79.
16. White HS, Brown SD, Woodhead JH, et al. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia 2000; 41(suppl 1): S17-20.
17. Gibbs JW, Sombati S, DeLorenzo RJ, et al. Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia 2000; 41(suppl 1): S10-6.
18. Skradski S, White HS. Topiramate blocks kainate-evoked cobalt influx into cultured neurons. Epilepsia 2000; 41(suppl 1): S45-7.
19. Gryder DS, Rogawski MA. Selective antagonism of GluR5 kainatereceptor- mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J Neurosci 2003; 23: 7069-74.
20. Zhang X, Velumian AA, Jones OT, et al. Modulation of highvoltage- activated calcium channels in dentate granule cells by topiramate. Epilepsia 2000; 41(suppl 1): S52-60.
21. Taverna S, Sancini G, Mantegazza M, et al. Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate. J Pharmacol Exp Ther 1999; 288: 960-8.
22. Herrero AI, Del Olmo N, Gonzalez-Escalada JR, et al. Two new actions of topiramate: inhibition of depolarizing GABA(A)- mediated responses and activation of a potassium conductance. Neuropharmacology 2002; 42: 210-20.
23. Dodgson SJ, Shank RP, Maryanoff BE. Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia 2000; 41(suppl 1): S35-9.
24. Shank RP, Gardocki JF, Streeter AJ, et al. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000; 41(suppl 1): S3-9.
25. Perucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine. Clin Pharmacokinet 1996; 31: 29-46.
26. Garnett WR. Clinical pharmacology of topiramate: a review. Epilepsia 2000; 41(suppl 1): S61-5.
27. Mula M. Anticonvulsants - antidepressants pharmacokinetic drug interactions: the role of the CYP450 system in psychopharmacology. Curr Drug Metab 2008; 9: 730-7.
28. Rosenfeld WE, Liao S, Kramer LD, et al. Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy. Epilepsia 1997; 38: 324-33.
29. Sachdeo RC, Sachdeo SK, Levy RH, et al. Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Epilepsia 2002; 43: 691-6.
30. Sachdeo RC, Sachdeo SK, Walker SA, et al. Steady-state pharmacokinetics of topiramate and carbamazepine in patients with epilepsy during monotherapy and concomitant therapy. Epilepsia 1996; 37: 774-80.
31. Doose DR, Brodie MJ, Wilson EA, et al. Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients. Epilepsia 2003; 44: 917-22.
32. Doose DR, Wang SS, Padmanabhan M, et al. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 2003; 44: 540-9.
33. Rosenfeld WE, Doose DR, Walker SA, et al. Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997; 38: 317-23.
34. Johnson BA. Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function. CNS Drugs 2005; 19: 873-96.
35. Doose DR, Kohl KA, Desai-Krieger D, et al. No clinically significant effect of topiramate on haloperidol plasma concentration. Poster presented at the European College of Neuropsychopharmacology (ECNP) congress. London, United Kingdom. September 21-25, 1999.
36. Doose DR, Kohl KA, Desai-Krieger D, et al. No significant effect of topiramate on lithium serum concentration. Poster presented at the World Congress of Psychiatry (WPA). Hamburg, Germany 1999.
37. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs, II: treatment of refractory epilepsy: report of the TTA and QSS subcommittees of the american academy of neurology and the american epilepsy society. Epilepsia 2004; 45: 410-23.
38. Wenzel RG, Schwarz K, Padiyara RS. Topiramate for migraine prevention. Pharmacotherapy 2006; 26: 375-87.
39. Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 2003; 361: 1677-85.
40. Rubio G, Ponce G, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F. Effects of topiramate in the treatment of alcohol dependence. Pharmacopsychiatry 2004; 37: 37-40.
41. Roy Chengappa KN, Levine J, Rathore D, et al. Long-term effects of topiramate on bipolar mood instability, weight change and glycemic control: a case-series. Eur Psychiatry 2001; 16: 186-90.
42. Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11: 722-33.
43. McElroy SL, Arnold LM, Shapira NA, et al. Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial. Am J Psychiatry 2003; 160: 255- 61.
44. Alderman CP, McCarthy LC, Condon JT, et al. Topiramate in combat-related posttraumatic stress disorder. Ann Pharmacother 2009; 43: 635-41.
45. Johnson BA. Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findings. Biochem Pharmacol 2008; 75: 34-56.
46. Biton V, Edwards KR, Montouris GD, et al. Topiramate TPS-TR Study Group. Topiramate titration and tolerability. Ann Pharmacother 2001; 35: 173-9.
47. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramateassociated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology 2004; 111: 109-11.
48. Desai CM, Ramchandani SJ, Bhopale SG, et al. Acute myopia and angle closure caused by topiramate, a drug used for prophylaxis of migraine. Indian J Ophthalmol 2006; 54: 195-7.
49. Guier CP. Elevated intraocular pressure and myopic shift linked to topiramate use. Optom Vis Sci 2007; 84: 1070-3.
50. Boonyaleephan S. Bilateral acute onset myopia and angle closure glaucoma after oral topiramate: a case report. J Med Assoc Thai 2008; 91: 1904-7.
51. Sbeity Z, Gvozdyuk N, Amde W, et al. Argon laser peripheral iridoplasty for topiramate-induced bilateral acute angle closure. J Glaucoma 2009; 18: 269-71.
52. Gawley SD. Topiramate induced acute transient myopia: a case report. Cases J 2009; 2: 7430.
53. Kuo RL, Moran ME, Kim DH, et al. Topiramate-induced nephrolithiasis. J Endourol 2002; 16: 229-31.
54. Ortho-McNeil Pharmaceutical I. Topamax® [package insert]. Raritan, NJ, Ortho-McNeil Pharmaceutical, Inc. 2008.
55. Ben-Zeev B, Watemberg N, Augarten A, et al. Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect. J Child Neurol 2003; 18: 254-7.
56. Dodson WE, Kamin M, Kraut L, et al. Topiramate titration to response: analysis of individualized therapy study (TRAITS). Ann Pharmacother 2003; 37: 615-20.
57. Johnson BA. Progress in the development of topiramate for treating alcohol dependence: from a hypothesis to a proof-of-concept study. Alcohol Clin Exp Res 2004; 28: 1137-44.
58. Carlezon WA, Jr., Nestler EJ. Elevated levels of GluR1 in the midbrain: a trigger for sensitization to drugs of abuse? Trends Neurosci 2002; 25: 610-5.
59. Laviolette SR, Gallegos RA, Henriksen SJ, et al. Opiate state controls bi-directional reward signaling via GABAA receptors in the ventral tegmental area. Nat Neurosci 2004; 7: 160-9.
60. Murray TD, Berger A. Alcohol withdrawal. Va Med Q 1997; 124: 184-9.
61. Engberg G, Hajos M. Alcohol withdrawal reaction as a result of adaptive changes of excitatory amino acid receptors. Naunyn- Schmiedebergs Arch Pharmacol 1992; 346: 437-41.
62. Tsai G, Coyle JT. The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Annu Rev Med 1998; 49: 173- 84.
63. Ennis M, Aston-Jones G. A potent excitatory input to the nucleus locus coeruleus from the ventrolateral medulla. Neurosci Lett 1986; 71: 299-305.
64. Ennis M, Aston-Jones G. Activation of locus coeruleus from nucleus paragigantocellularis: a new excitatory amino acid pathway in brain. J Neurosci 1988; 8: 3644-57.
65. Kawahara Y, Kawahara H, Westerink BH. Tonic regulation of the activity of noradrenergic neurons in the locus coeruleus of the conscious rat studied by dual-probe microdialysis. Brain Res 1999; 823: 42-8.
66. Erhardt S, Hajos M, Lindberg A, et al. Nicotine-induced excitation of locus coeruleus neurons is blocked by elevated levels of endogenous kynurenic acid. Synapse 2000; 37: 104-8.
67. Rasmussen K, Vandergriff J. The selective iGluR1-4 (AMPA) antagonist LY300168 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioural signs of morphine withdrawal. Neuropharmacology 2003; 44: 88-92.
68. Schiffer WK, Gerasimov MR, Marsteller DA, et al. Topiramate selectively attenuates nicotine-induced increases in monoamine release. Synapse 2001; 42: 196-8.
69. Cagetti E, Baicy KJ, Olsen RW. Topiramate attenuates withdrawal signs after chronic intermittent ethanol in rats. Neuroreport 2004; 15: 207-10.
70. Smith L, Price-Jones M, Hughes K, et al. Effects of topiramate on kainate- and domoate-activated [14C]guanidinium ion flux through GluR6 channels in transfected BHK cells using Cytostar-T scintillating microplates. Epilepsia 2000; 41(suppl 1): S48-51.
71. Koob GF. Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 2003; 27: 232-43.
72. Rustembegovic A, Sofic E, Kroyer G. A pilot study of topiramate (Topamax) in the treatment of tonic-clonic seizures of alcohol withdrawal syndromes. Med Arch 2002; 56: 211-2.
73. Krupitsky EM, Rudenko A, Zvartau E, et al. The pilot study of topiromate for alcohol withdrawal syndrome [abstract]. Alcohol Alcohol 2003; 38: 508-9.
74. Gabriel KI, Cunningham CL. Effects of topiramate on ethanol and saccharin consumption and preferences in C57BL/6J mice. Alcohol Clin Exp Res 2005; 29: 75-80.
75. Nguyen SA, Malcolm R, Middaugh LD. Topiramate reduces ethanol consumption by C57BL/6 mice. Synapse 2007; 61: 150-6.
76. Farook JM, Lewis B, Littleton JM, et al. Topiramate attenuates the stress-induced increase in alcohol consumption and preference in male C57BL/6J mice. Physiol Behav 2009; 96: 189-93.
77. Breslin FJ, Johnson BA, Lynch WJ. Effect of topiramate treatment on ethanol consumption in rats. Psychopharmacology 2010; 207: 529-34.
78. Farook JM, Morrell DJ, Lewis B, et al. Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster mice. Alcohol Alcohol 2007; 42: 296-300.
79. Johnson BA, Mann K, Willenbring ML, et al. Challenges and opportunities for medications development in alcoholism: an international perspective on collaborations between academia and industry. Alcohol Clin Exp Res 2005; 29: 1528-40.
80. Miranda RJ, MacKillop J, Monti PM, et al. Effects of topiramate on urge to drink and the subjective effects of alcohol: a preliminary laboratory study. Alcohol Clin Exp Res 2008; 32: 489-97.
81. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington, D.C.: American Psychiatric Association 1994.
82. Johnson BA, DiClemente CC, Ait-Daoud N, et al. Brief Behavioral Compliance Enhancement Treatment (BBCET) manual. In: Johnson BA, Ruiz P, Galanter M, Eds. Handbook of clinical alcoholism treatment. Baltimore, MD: Lippincott Williams & Wilkins 2003; pp. 282-301.
83. Fawcett J, Epstein P, Fiester SJ, et al. Clinical management - imipramine/placebo administration manual: NIMH treatment of depression collaborative research program. Psychopharmacol Bull 1987; 23: 309-24.
84. Edwards G, Orford J, Egert S, et al. Alcoholism: a controlled trial of 'treatment' and 'advice'. J Stud Alcohol 1977; 38: 1004-31.
85. Conigrave KM, Degenhardt LJ, Whitfield JB, et al. WHO/ISBRA Study Group. CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcohol Clin Exp Res 2002; 26: 332-9.
86. Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res 1995; 19: 92-9.
87. Bohn MJ, Barton BA, Barron KE. Psychometric properties and validity of the obsessive-compulsive drinking scale. Alcohol Clin Exp Res 1996; 20: 817-23.
88. Johnson BA, Ait-Daoud N, Akhtar FZ, et al. Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals. Arch Gen Psychiatry 2004; 61: 905-12.
89. Ma JZ, Ait-Daoud N, Johnson BA. Topiramate reduces the harm of excessive drinking: implications for public health and primary care. Addiction 2006; 101: 1561-8.
90. Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 2007; 298: 1641-51.
91. First MB, Spitzer RL, Gibbon M, et al. Structured Clinical Interview for DSM-IV Axis I Disorders - Patient Edition (SCID-I/P, Version 2.0). New York: New York State Psychiatric Institute, Biometrics Research Department 1997.
92. Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989; 84: 1353-7.
93. Johnson BA, Rosenthal N, Capece JA, et al. Improvement of physical health and quality of life of alcohol-dependent individuals with topiramate treatment. Arch Intern Med 2008; 168: 1188-99.
94. Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for the treatment of alcohol dependence: results of a multi-site trial. New Research Poster presented at the 160th Annual Meeting of the American Psychiatric Association, San Diego May 22, 2007.
95. Baltieri DA, Daró FR, Ribeiro PL, et al. Comparing topiramate with naltrexone in the treatment of alcohol dependence. Addiction 2008; 103: 2035-44.
96. Flórez G, García-Portilla P, Álvarez S, et al. Using topiramate or naltrexone for the treatment of alcohol-dependent patients. Alcohol Clin Exp Res 2008; 32: 1251-9.
97. Fagerström KO. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 1978; 3: 235-41.
98. De Sousa AA, De Sousa JA, Kapoor H. An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence. J Subst Abuse Treat 2008; 34: 460-3.
99. Rubio G, Martínez-Gras I, Manzanares J. Modulation of impulsivity by topiramate: implications for the treatment of alcohol dependence. J Clin Psychopharmacol 2009; 29: 584-9.
100. Logan GD. On the ability to inhibit thought and action: a users' guide to the stop signal paradigm. In: Dagenbach D, Carr TH, Eds. Inhibitory processes in attention, memory and language. San Diego: Academic Press 1994; pp. 189-239.
101. Conners CK. Conners' Continuous Performance Test computer program 3.0: users manual. Toronto, Ontario, Canada: Multi-Health Systems, Inc. 1995.
102. Ray LA, Miranda R, Jr., MacKillop J, et al. A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers. Exp Clin Psychopharmacol 2009; 17: 122-9.
103. Kuehn BM. New therapies for alcohol dependence open options for office-based treatment. JAMA 2007; 298: 2467-8.
104. Aldhous P. Prescription: sobriety. New Scientist 2010; 205(2742): 40-3.
105. Christmas D, Hood S, Nutt D. Potential novel anxiolytic drugs. Curr Pharm Des. 2008; 14(33): 3534-46.
106. Domschke K, Zwanzger P. GABAergic and endocannabinoid dysfunction in anxiety - future therapeutic targets? Curr Pharm Des. 2008; 14(33): 3508-17.
107. Wang LL, Yang AK, He SM, et al. Identification of Molecular Targets Associated With Ethanol Toxicity and Implications in Drug Development. Curr Pharm Des. 2010; 16(11): 1315-55.