Anticonvulsant efficacy of valproate-like carboxylic acids: a potential target for anti-bipolar therapy
Abed N Azab,
Miriam L Greenberg,
Abed N Azab
Department of Biological Sciences, Wayne State University, Detroit, MI, USA
Search for more papers by this authorMiriam L Greenberg
Department of Biological Sciences, Wayne State University, Detroit, MI, USA
Search for more papers by this authorAbed N Azab,
Miriam L Greenberg,
Abed N Azab
Department of Biological Sciences, Wayne State University, Detroit, MI, USA
Search for more papers by this authorMiriam L Greenberg
Department of Biological Sciences, Wayne State University, Detroit, MI, USA
Search for more papers by this authorMiriam L Greenberg, Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA. Fax: + 1 313 577 6891; e-mail: [email protected]
The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.
Abstract
Background: Bipolar disorder (BPD) is a severe and chronic illness, with a lifetime prevalence of approximately 1.5%. Despite the availability of some mood stabilizing drugs including lithium, valproate (valproic acid), lamotrigine and carbamazepine, BPD is characterized by high rates of recurrence, as treatment with these and other drugs is ineffective for and not well-tolerated by a significant percentage of patients. Most drugs currently used for the maintenance treatment of BPD are anticonvulsants (e.g., valproate, carbamazepine and lamotrigine).
Objectives: The aim of this paper is to review the studies characterizing the anticonvulsant efficacy of valproate-like carboxylic acids and related compounds, some of which may have potential for the treatment of manic-depressive illness.
Results: The data reviewed herein demonstrate clearly that some dietary fatty acids and other valproate-like carboxylic acids exhibit potent anticonvulsant activity, and may thus be candidates for mood stabilizing treatment options for BPD.
References
- 1 Narrow WE, Rae DS, Robins LN. Revised prevalence estimates of mental disorders in the United States: using clinical significance criterion to reconcile two surveys’ estimates. Arch Gen Psychiatry 2002; 59: 115–123.
- 2 Murray CJL, Lopez AD, eds. The Global Burden of Disease. Cambridge, MA: Harvard University Press, 1996.
- 3 Belmaker RH. Bipolar disorder. N Engl J Med 2004; 351: 476–486.
- 4 Nemeroff CB. Safety of available agents used to treat bipolar disorder: focus on weight gain. J Clin Psychiatry 2003; 64: 532–529.
- 5 Bowden CL. Making optimal use of combination pharmacotherapy in bipolar disorder. J Clin Psychiatry 2004; 65: 21–24.
- 6 Berridge MJ, Downes CP, Hanley MR. Lithium amplifies agonist-dependent phosphatidyl-inositol responses in brain and salivary glands. Biochem J 1982; 206: 587–595.
- 7 Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature 1989; 341: 197–204.
- 8 Sterb H, Irvine RF, Berridge MJ, Schulz I. Release of Ca+2 from non-mitochondrial store in pancreatic acinar cells by inositol-1,4,5-triphosphate. Nature 1983; 306: 67–69.
- 9 Irvine RF, Letcher AJ, Lander DJ, Downes CP. Inositol triphosphates in carbachol-stimulated rat parotid glands. Biochem J 1984; 223: 237–243.
- 10 Irvine RF, Schell MJ. Back in the water: the return of the inositol phosphates. Nature Rev 2001; 2: 327–338.
- 11 Berridge MJ. Inositol triphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem 1987; 56: 159–193.
- 12 Hallcher LM, Sherman WR. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem 1980; 255: 10896–11091.
- 13 Naccarato WF, Ray RE, Wells WW. Biosynthesis of myo-inositol in rat mammary gland. Isolation and properties of the enzymes. Arch Biochemica Biophysica 1974; 164: 194–201.
- 14 Inhorn RC, Majerus PW. Properties of inositol polyphosphate 1-phosphatase. J Biol Chem 1988; 263: 14559–14565.
- 15 Attack JR. Lithium, phosphatidylinositol signaling, and bipolar disorder. The role of inositol monophosphatase. In: HK Manji, CL Bowden, RH Belmaker, eds. Bipolar Medications: Mechanism of Action. Washington DC: American Psychiatric Press, Inc., 2000: 1–30.
- 16 Moore GJ, Bebchunk JM, Parrish JK et al. Temporal dissociation between lithium-induced changes in frontal lobe myo-inositol and clinical response in manic-depressive illness. Am J Psychiatry 1999; 156: 1902–1908.
- 17 Silverstone PH, Wu RH, O'Donnell T, Ulrich M, Asghar SJ, Handstock CC. Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients. Human Psychopharmacol 2002; 17: 321–327.
- 18 Klein PS, Milton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 1996; 93: 8455–8459.
- 19 Pollack SJ, Atack JR, Knowles MR et al. Mechanism of inositol monophosphatase, the putative target of lithium therapy. Proc Natl Acad Sci U S A 1994; 91: 5766–5770.
- 20 Jope RS. Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol Sci 2003; 24: 441–443.
- 21 Gould TD, Quiroz JA, Singh J, Zarate CA Jr, Manji HK. Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood-stabilizers. Mol Psychiatry 2004; 9: 734–755.
- 22 Gould TD, Zarate CA Jr Manji HK. Glycogen synthase kinase-3: a target for novel bipolar disorder treatment. J Clin Psychiatry 2004; 65: 10–21.
- 23 Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H. Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry 2004; 55: 781–784.
- 24 Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol 2004; 26: 1–4.
- 25 Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry 1999; 46: 929–940.
- 26 Chen G, Huang LD, Jiang YM, Manji HK. The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J Neurochem 1999; 72: 1327–1330.
- 27 Chen G, Zeng WZ, Yuan PX et al. The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem 1999; 72: 879–882.
- 28 Vaden DL, Ding D, Peterson B, Greenberg ML. Lithium and valproate decrease inositol mass and increase expression of the yeast INO1 and INO2 genes for inositol biosynthesis. J Biol Chem 2001; 276: 15466–15471.
- 29 Williams RSB, Cheng L, Mudge AW, Harwood AJ. A common mechanism of action for three mood-stabilizing drugs. Nature 2002; 417: 292–295.
- 30 Ju S, Shaltiel G, Shamir A, Agam G, Greenberg ML. Human 1-d-myo-inositol-3-phosphate synthase is functional in yeast. J Biol Chem 2004; 279: 21759–21765.
- 31 Loewus MW, Loewus FA, Brillinger GU, Otsuka H, Floss HG. Stereochemistry of the myo-inositol-1-phosphate synthase reaction. J Biol Chem 1980; 255: 11710–11712.
- 32 Shaltiel G, Shamir A, Shapiro J et al. Valproate decreases inositol biosynthesis. Mol Psychiatry 2004; 56: 868–874.
- 33 Bowden CL, Brugger AM, Swann AC et al. Efficacy of divalproex versus lithium and placebo in the treatment of mania. JAMA 1994; 271: 918–924. [Erratum: JAMA 1994; 271: 1830].
- 34 Bowden CL, Calabrese JR, McElroy SL et al. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Arch Gen Psychiatry 2000; 57: 481–489.
- 35 Okuma T, Inanaga K, Otsuki S et al. A preliminary double-blind study on the efficacy of carbamazepine in prophylaxis of manic-depressive illness. Psychopharmacology (Berl) 1981; 73: 95–96.
- 36 Ketter TA, Post RM, Denicoff K et al. Carbamazepine. In: PJ Goodnick, ed. Mania: Clinical and Research Perspectives. Washington DC: American Psychiatric Press, 1998: 263–300.
- 37 Calabrese JR, Bowden CL, Sachs G et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry 2003; 64: 1013–1024.
- 38 Mishory A, Yaroslavsky Y, Bersudsky Y, Belmaker RH. Phenytoin as an antimanic anticonvulsant: a controlled study. Am J Psychiatry 2000; 157: 463–465.
- 39 Mishory A, Winokur M, Bersudsky Y. Prophylactic effect of phenytoin in bipolar disorder: a controlled study. Bipolar Disord 2003; 5: 464–467.
- 40 Yatham LN, Kusumakar V, Calabrese JR, Rao R, Scarrow G, Kroeker G. Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations. J Clin Psychiatry 2002; 63: 275–283.
- 41 Keane PE, Simiand J, Mendes E, Santucci V, Morre M. The effects of analogues of valproic acid on seizures induced by pentylenetetrazol and GABA content in brain of mice. Neuropharmacology 1983; 22: 875–879.
- 42 National Academic Press. Dietary Reference Intakes for Energy, Carbohydrates, Fibre, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids (Macronutrients). Washington, DC: National Academic Press, 2002: 335–432.
- 43 Chug Ahuja JK, Exler J, Raper N. USDA Data Tables for Individual Fatty Acids Intakes. Results from the 1995 Continuing Survey of Food Intakes by Individuals, 1998; http://www.barc.usda.gov/bhnrc/foodsurvey/home.htm .
- 44 Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 2002; 16: 695–714.
- 45 Liu MJ, Pollack GM. Pharmacokinetics and pharmacodynamics of valproate analogues in rats. IV. Anticonvulsant action and neurotoxicity of octanoic acid, cyclohexane carboxylic acid, and 1-methyl-1-cyclohexane carboxylic acid. Epilepsia 1994; 35: 234–243.
- 46 Chapman A, Keane PE, Meldrum BS, Simiand J, Vernieres JC. Mechanism of anticonvulsant action of valproate. Prog Neurobiol 1982; 19: 315–359.
- 47 Bialer M, Hadad S, Kadry B et al. Pharmacokinetic analysis and antiepileptic activity of tetra-methylcyclopropane analogues of valpromide. Pharmacol Res 1996; 13: 284–289.
- 48 Isoherranen N, White HS, Finnell RH et al. Anticonvulsant profile and teratogenicity of N-methyl-tetramethyl-cyclopropyl carboxamide: a new antiepileptic drug. Epilepsia 2002; 43: 115–126.
- 49 Redecker C, Altrup U, Hoppe D, Dusing R, Speckmann EJ. Effects of valproate derivatives I. Antiepileptic efficacy of amides, structural analogues and esters. Neuropharmacology 2000; 39: 254–266.
- 50 Morre M, Keane PE, Vernieres JC, Simiand J, Roncucci R. Valproate: recent findings and perspective. Epilepsia 1984; 25 (Suppl. 1): 5–9.
- 51 Roden DM. Antiarrhythmic drugs. In: JG Hardman, LE Limbird, AG Gilman, eds. Goodman and Gilman's Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 2001: 933–970.
- 52 McNamara JQ. Drugs effective in the therapy of the epilepsies. In: JG Hardman, LE Limbird, AG Gilman, eds. Goodman and Gilman's Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 2001: 521–548.
- 53 Kang JX, Xiao YF, Leaf A. Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes. Proc Natl Acad Sci U S A 1995; 92: 3997–34001.
- 54 Leaf A, Kang JX, Xiao YF, Billman GE. N-3 fatty acids in the prevention of cardiac arrhythmias. Lipids 1999; 34: S187–S189.
- 55 Xiao YF, Gomez AM, Morgan JP, Lederer WJ, Leaf A. Suppression of voltage-gated 1-type Ca2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes. Proc Natl Acad Sci U S A 1997; 94: 4182–4187.
- 56
Petit-Jacues J,
Hartzell HC.
Effect of arachidonic acid on the 1-type calcium current in frog cardiac myocytes.
J Physiol (London)
1996; 493: 67–81.
10.1113/jphysiol.1996.sp021365 Google Scholar
- 57 Mclean MJ, MacDonald RL. Multiple actions of phenytoin on mouse spinal cord neurons in cell culture. J Pharmacol Exp Therapeutics 1983; 227: 779–789.
- 58 Mclean MJ, MacDonald RL. Sodium valproate, but not ethosuxmide, produces use and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture. J Pharmacol Exp Therapeutics 1986; 237: 1001–1010.
- 59 Voskuyl RA, Vreudenhil M, Kang JX, Leaf A. Anticonvulsant effect of polyunsaturated fatty acids in rats, using the cortical stimulation model. Eur J Pharmacol 1998; 341: 145–152.
- 60 Yehuda S, Carasso RF, Mostofsky DI. Essential fatty acids preparation (SR-3) raises the seizure threshold in rats. Eur J Pharmacol 1994; 254: 193–198.
- 61 Nakashima Y, Yuasa S, Hukamizu Y et al. Effect of a high linoleate and a high alpha-linoleate diet on general behaviour and drug sensitivity in mice. J Lipid Res 1993; 34: 239–247.
- 62 Lands WEM. Fish and Human Health. Orlando, FL: Academic Press 1986.
- 63 Ward GR, Huang YS, Xing HC et al. Effects of gamma-linolenic acid and docosahexaenoic acid in formulae on brain fatty acid composition in artificially reared rats. Lipids 1999; 34: 1057–1063.
- 64 Wainwright PE. Do essential fatty acids play a role in brain and behavioural development? Neurosci Behav Rev 1992; 16: 193–205.
- 65 Vining EP, Freeman JM, Ballaban-Gil K et al. A multicentre study of the efficacy of the ketogenic diet. Arch Neurol 1998; 55: 1433–1437.
- 66 Vining EP. Clinical efficacy of the ketogenic diet. Epilepsy Res 1999; 37: 181–190.
- 67 Geyelin HR. Fasting as a method for treating epilepsy. Med Res 1921; 99: 1037–1039.
- 68 Appleton DB, DeVivo DC. An animal model for the ketogenic diet. Epilepsia 1974; 15: 211–227.
- 69 Bough KJ, Eagles DA. A ketogenic diet increases the resistance to pentylenetetrazole-induced seizures in the rat. Epilepsia 1999; 40: 138–143.
- 70 Uhlemann ER, Neims AH. Anticonvulsant properties of the ketogenic diet in mice. J Pharmacol Exp Therapeutic 1972; 180: 231–238.
- 71 Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics 1998; 102: 1358–1363.
- 72 Bough KJ, Eagles DA. Comparison of the anticonvulsant efficacies and neurotoxic effects of valproic acid, phenytoin, and the ketogenic diet. Epilepsia 2001; 42: 1345–1353.
- 73 Goodwin FK, Jamison KR. Manic Depressive Illness. Oxford: Oxford University Press, 1990.
- 74 Gitlin MJ, Swendsen J, Heller TL, Hammen C. Relapse and impairment in bipolar disorder. Am J Psychiatry 1995; 152: 1635–1640.
- 75 Stoll AL, Severus WE, Freeman MP et al. Omega-3 fatty acids in bipolar disorder. A preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999; 56: 407–412.
- 76 Chen G, Manji HK, Hawver DB, Wright CB, Poter WZ. Chronic sodium valproate selectively decreases protein kinase C a and e in vitro. J Neurochem 1994; 63: 2361–2364.
- 77 Manji HK, Bersudsky Y, Chen G, Belmaker RH, Potter WZ. Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol. Neuropsychopharmacology 1996; 15: 370–381.
- 78 Stoll AL, Severus E. Mood-stabilizers: shared mechanisms of actions at post-synaptic signal transduction and kindling processes. Harvard Rev Psychiatry 1996; 4: 77–89.
- 79 Sperling RI, Benincaso AL, Knoell CT, Larkin JK, Austen KF, Robinson DR. Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 1993; 91: 651–660.
- 80 Tappia PS, Ladha S, Clark DC, Grimble RF. The influence of membrane fluidity, TNF receptor binding, cAMP production and GTPase activity on macrophage cytokine production in rats fed a variety of fat diets. Mol Cell Biochem 1997; 166: 135–143.
- 81 Robert E, Rosa F. Valproate and birth defects. Lancet 1983; 2: 1142.
- 82 Colletti RB, Trainer TD, Krawisz BR. Reversible valproate fulminant hepatic failure. J Pediatr Gastroenterol Nutr 1986; 5: 990–994.
- 83 Nau H, Hauck RS, Ehlers K. Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacol Toxicol 1991; 69: 310–321.
- 84 Palaty J, Abbott S. Structure–activity relationship of unsaturated analogues of valproic acid. J Med Chem 1995; 38: 3398–3406.
- 85 Bojic U, Elmazar MMA, Hauck RS, Nau H. Further branching of valproate-related carboxylic acids reduces the teratogenic activity, but not the anticonvulsant effect. Chem Res Toxicol 1996; 9: 866–870.
- 86 Isoherranen N, Yagen B, Bialer M. New CNS-active drugs which are second-generation valproic acid: can they lead to the development of a magic bullet? Curr Opin Neurol 2003; 16: 203–211.
- 87 Dusing RH. Single-dose tolerance and pharmacokinetics of 2-n-propyl-delta-2-(E) -pentanoate (delta-2 (E) valproate) in healthy male volunteers. Pharmaceutisch Weekblad Scientific Edition 1992; 20: 114–122.
- 88 Loescher W. Pharmacological, toxicological and neurochemical effects of delta-2(E) valproate in animals. Pharmaceutisch Weekblad Scientific Edition 1992; 14: 139–143.
- 89 Sokolova S, Schmitz D, Zhang CL, Loscher W, Heinemann U. Comparison of effects of valproate and trans-2-n-valproate on different forms of epileptiform activity in rat hippocampal and temporal cortex slices. Epilepsia 1998; 39: 251–258.
