Novel analogues of chlormethiazole are neuroprotective in four cellular models of neurodegeneration by a mechanism with variable dependence on GABA A receptor potentiation

British Journal of Pharmacology

Volumn 171, Issue 2, 2014, Pages 389-402

  Vandevrede, Lawren ^a   Tavassoli, Ehsan ^a   Luo, Jia ^a   Qin, Zhihui ^a   Yue, Lan ^a,b   Pepperberg, David R ^a,b   Thatcher, Gregory R ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b University of Illinois at Chicago   (United States)

Author keywords

Alzheimer's disease; chlormethiazole; excitotoxicity; GABA; GABAA receptor; neurodegeneration; neuroprotection; stroke

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR ALPHA1; 4 AMINOBUTYRIC ACID A RECEPTOR BETA2; 4 AMINOBUTYRIC ACID A RECEPTOR GAMMA2; CALCIUM; CLOMETHIAZOLE; GLUTAMIC ACID; GN 28; GN 38; NEUROPROTECTIVE AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CALCIUM CELL LEVEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG MECHANISM; DRUG PENETRATION; DRUG STRUCTURE; FEMALE; IN VITRO STUDY; MALE; MOUSE; NEUROPROTECTION; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; RAT;

ALZHEIMER'S DISEASE; CHLORMETHIAZOLE; EXCITOTOXICITY; GABA; GABAA RECEPTOR; NEURODEGENERATION; NEUROPROTECTION; STROKE;

ANIMALS; BIOLOGICAL AVAILABILITY; BRAIN; CALCIUM; CELL HYPOXIA; CHLORMETHIAZOLE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; EXCITATORY AMINO ACID AGONISTS; FEMALE; GABA AGONISTS; GAMMA-AMINOBUTYRIC ACID; GLUCOSE; GLUTAMIC ACID; MICE; MICE, INBRED C57BL; N-METHYLASPARTATE; NERVE DEGENERATION; NEURONS; NEUROPROTECTIVE AGENTS; OOCYTES; PREGNANCY; PRIMARY CELL CULTURE; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GABA-A; XENOPUS LAEVIS;

EID: 84891277860     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12454     Document Type: Article

References (59)

1. Abdelhamid R, Luo J, VandeVrede L, Kundu I, Michalsen B, Litosh VA, et al. (2011). Benzothiophene selective estrogen receptor modulators provide neuroprotection by a novel GPR30-dependent mechanism. ACS Chem Neurosci 2: 256-268.
2. Alexander SPH, et al. (2013). The Concise Guide to PHARMACOLOGY 2013/14: Overview. Br J Pharmacol 170: 1449-1867.
3. Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M, (2007). Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging 28: 533-536. (Pubitemid 46282207)
4. Baldwin HA, Williams JL, Snares M, Ferreira T, Cross AJ, Green AR, (1994). Attenuation by chlormethiazole administration of the rise in extracellular amino acids following focal ischaemia in the cerebral cortex of the rat. Br J Pharmacol 112: 188-194. (Pubitemid 24151725)
5. Bengtsson S, Lindberg UH, (1982). Compounds related to clomethiazole. VI. Synthesis of some reference compounds in connection with biotransformation studies. Acta Pharm Suec 19: 37-42. (Pubitemid 12152323)
6. Brito-Moreira J, Paula-Lima AC, Bomfim TR, Oliveira FB, Sepulveda FJ, De Mello FG, et al. (2011). Abeta oligomers induce glutamate release from hippocampal neurons. Curr Alzheimer Res 8: 552-562.
7. Clarkson AN, Liu H, Rahman R, Jackson DM, Appleton I, Kerr DS, (2005). Clomethiazole: mechanisms underlying lasting neuroprotection following hypoxia-ischemia. FASEB J 19: 1036-1038. (Pubitemid 40827743)
8. Clarkson AN, Clarkson J, Jackson DM, Sammut IA, (2007). Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: clomethiazole-mediated amelioration. Neuroscience 144: 547-561. (Pubitemid 44855307)
9. Colado MI, O'Shea E, Esteban B, Green AR, (2001). Studies on the neuroprotective effect of the enantiomers of AR-A008055, a compound structurally related to clomethiazole, on MDMA ('ecstasy')-induced neurodegeneration in rat brain. Psychopharmacology (Berl) 157: 82-88. (Pubitemid 32758963)
10. Cross AJ, Stirling JM, Robinson TN, Bowen DM, Francis PT, Green AR, (1989). The modulation by chlormethiazole of the GABAA-receptor complex in rat brain. Br J Pharmacol 98: 284-290. (Pubitemid 19225232)
11. Cross AJ, Jones JA, Snares M, Jostell KG, Bredberg U, Green AR, (1995). The protective action of chlormethiazole against ischaemia-induced neurodegeneration in gerbils when infused at doses having little sedative or anticonvulsant activity. Br J Pharmacol 114: 1625-1630.
12. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, et al. (2007). Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 282: 11590-11601. (Pubitemid 47100810)
13. De Keyser J, Sulter G, Luiten PG, (1999). Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? Trends Neurosci 22: 535-540.
14. Farooque M, Isaksson J, Jackson DM, Olsson Y, (1999). Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat. Acta Neuropathol (Berl) 98: 22-30. (Pubitemid 29278305)
15. Gladstone DJ, Black SE, Hakim AM, (2002). Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions. Stroke 33: 2123-2136. (Pubitemid 34840080)
16. Green AR, (1998). Clomethiazole (Zendra) in acute ischemic stroke: basic pharmacology and biochemistry and clinical efficacy. Pharmacol Ther 80: 123-147. (Pubitemid 28498225)
17. Green AR, Hainsworth AH, Jackson DM, (2000). GABA potentiation: a logical pharmacological approach for the treatment of acute ischaemic stroke. Neuropharmacology 39: 1483-1494. (Pubitemid 30330866)
18. Green AR, Hainsworth AH, Misra A, Debens TA, Jackson DM, Murray TK, et al. (2001). The interaction of AR-A008055 and its enantiomers with the GABA(A) receptor complex and their sedative, muscle relaxant and anticonvulsant activity. Neuropharmacology 41: 167-174. (Pubitemid 32728088)
19. Haass C, Selkoe DJ, (2007). Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8: 101-112. (Pubitemid 46432529)
20. Hankey GJ, (2002). Clomethiazole: an unsuccessful bachelor, but perhaps a prosperous married man? Stroke 33: 128-129. (Pubitemid 34052198)
21. Harmon D, Coleman E, Marshall C, Lan W, Shorten G, (2003). The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Anesth Analg 97: 13-18. (Pubitemid 36736530)
22. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577-1579.
23. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, et al. (1998). Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A 95: 6448-6453.
24. Lechat P, Streichenberger G, Boime A, Lemeignan M, (1965a). Relation between chemical structure and physiological activity of certain thiazole derivatives. I. 4-Methyl-5-(b-hydroxyethyl)thiazole. Ann Pharm Franc 23: 179-186.
25. Lechat P, Streichenberger G, Boime A, Lemeignan M, (1965b). Relations between the chemical structure and physiological activity of certain thiazole derivatives. II. Effect of the length of the alkyl chain in 4-methyl-5-(w- chloroalkyl)thiazoles. Ann Pharm Franc 23: 369-576.
26. Lechat P, Van Den Driessche J, Lemeignan M, Deleau D, (1965c). Pharmacological investigation of a quaternary ammonium compound with ganglion-exciting properties. Arch Int Pharmacodyn Ther 155: 262-272.
27. Liang SP, Kanthan R, Shuaib A, Wishart T, (1997). Effects of clomethiazole on radial-arm maze performance following global forebrain ischemia in gerbils. Brain Res 751: 189-195. (Pubitemid 27132548)
28. Limon A, Reyes-Ruiz JM, Miledi R, (2012). Loss of functional GABA(A) receptors in the Alzheimer diseased brain. Proc Natl Acad Sci U S A 109: 10071-10076.
29. Lindberg UH, (1971a). Compounds related to clomethiazole. IV. 4-Methylthiazoles and oxazoles with polar side-chains and some other analogs of clomethiazole. Acta Pharm Suec 8: 39-48.
30. Lindberg UH, (1971b). Hypnotic and anticonvulsant agents related to the thiazole part of thiamine. Acta Pharm Suec 8: 647-660.
31. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
32. Marshall JW, Cross AJ, Ridley RM, (1999). Functional benefit from clomethiazole treatment after focal cerebral ischemia in a nonhuman primate species. Exp Neurol 156: 121-129. (Pubitemid 29152989)
33. Marshall JW, Cross AJ, Jackson DM, Green AR, Baker HF, Ridley RM, (2000). Clomethiazole protects against hemineglect in a primate model of stroke. Brain Res Bull 52: 21-29. (Pubitemid 30211624)
34. Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE, (1992). Beta-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12: 376-389.
35. McAlpine FE, Lee JK, Harms AS, Ruhn KA, Blurton-Jones M, Hong J, et al. (2009). Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuropathology. Neurobiol Dis 34: 163-177.
36. Mohler H, (2011). The rise of a new GABA pharmacology. Neuropharmacology 60: 1042-1049.
37. Moody EJ, Skolnick P, (1989). Chlormethiazole: neurochemical actions at the gamma-aminobutyric acid receptor complex. Eur J Pharmacol 164: 153-158. (Pubitemid 19124053)
38. Mucke H, (1999). Clomethiazole (Astra Arcus AB). Idrugs 2: 184-193.
39. Mucke L, Selkoe DJ, (2012). Neurotoxicity of amyloid beta-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med 2: a006338.
40. Muir KW, Grosset DG, (1999). Neuroprotection for acute stroke: making clinical trials work. Stroke 30: 180-182. (Pubitemid 29029460)
41. Nelson RM, Hainsworth AH, Lambert DG, Jones JA, Murray TK, Richards DA, et al. (2001). Neuroprotective efficacy of AR-A008055, a clomethiazole analogue, in a global model of acute ischaemic stroke and its effect on ischaemia-induced glutamate and GABA efflux in vitro. Neuropharmacology 41: 159-166. (Pubitemid 32728087)
42. Olsen RW, (1982). Drug interactions at the GABA receptor-ionophore complex. Annu Rev Pharmacol Toxicol 22: 245-277.
43. Qin Z, Luo J, VandeVrede L, Tavassoli E, Fa M, Teich AF, et al. (2012). Design and synthesis of neuroprotective methylthiazoles and modification as NO-chimeras for neurodegenerative therapy. J Med Chem 55: 6784-6801.
44. Rissman RA, Mobley WC, (2011). Implications for treatment: GABAA receptors in aging, down syndrome and Alzheimer's disease. J Neurochem 117: 613-622.
45. Rudolph U, Knoflach F, (2011). Beyond classical benzodiazepines: novel therapeutic potential of GABA(A) receptor subtypes. Nat Rev Drug Discov 10: 685-697.
46. Santos RX, Correia SC, Carvalho C, Cardoso S, Santos MS, Moreira PI, (2011). Mitophagy in neurodegeneration: an opportunity for therapy? Curr Drug Targets 12: 790-799.
47. Shi JQ, Shen W, Chen J, Wang BR, Zhong LL, Zhu YW, et al. (2011). Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res 1368: 239-247.
48. Snape MF, Baldwin HA, Cross AJ, Green AR, (1993). The effects of chlormethiazole and nimodipine on cortical infarct area after focal cerebral ischaemia in the rat. Neuroscience 53: 837-844. (Pubitemid 23114569)
49. Stine WB, Jr, Dahlgren KN, Krafft GA, Ladu MJ, (2003). In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J Biol Chem 278: 11612-11622. (Pubitemid 36792723)
50. Strum JC, Shehee R, Virley D, Richardson J, Mattie M, Selley P, et al. (2007). Rosiglitazone induces mitochondrial biogenesis in mouse brain. J Alzheimers Dis 11: 45-51. (Pubitemid 46376708)
51. Sydserff SG, Cross AJ, Green AR, (1995a). The neuroprotective effect of chlormethiazole on ischaemic neuronal damage following permanent middle cerebral artery ischaemia in the rat. Neurodegeneration 4: 323-328.
52. Sydserff SG, Cross AJ, West KJ, Green AR, (1995b). The effect of chlormethiazole on neuronal damage in a model of transient focal ischaemia. Br J Pharmacol 114: 1631-1635.
53. Usala M, Thompson SA, Whiting PJ, Wafford KA, (2003). Activity of chlormethiazole at human recombinant GABA(A) and NMDA receptors. Br J Pharmacol 140: 1045-1050. (Pubitemid 37475970)
54. Vellas B, Sol O, Snyder PJ, Ousset PJ, Haddad R, Maurin M, et al. (2011). EHT0202 in Alzheimer's disease: a 3-month, randomized, placebo-controlled, double-blind study. Curr Alzheimer Res 8: 203-212.
55. Wahlgren NG, Ranasinha KW, Rosolacci T, Franke CL, Van Erven PM, Ashwood T, et al. (1999). Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 30: 21-28. (Pubitemid 29029436)
56. Wahlgren NG, Diez-Tejedor E, Teitelbaum J, Arboix A, Leys D, Ashwood T, et al. (2000). Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients. Stroke 31: 82-85. (Pubitemid 30035757)
57. Wilby MJ, Hutchinson PJ, (2004). The pharmacology of chlormethiazole: a potential neuroprotective agent? CNS Drug Rev 10: 281-294. (Pubitemid 40128913)
58. Yu C, Nwabuisi-Heath E, Laxton K, Ladu MJ, (2010). Endocytic pathways mediating oligomeric Abeta42 neurotoxicity. Mol Neurodegener 5: 19.
59. Yue L, Pawlowski M, Dellal SS, Xie A, Feng F, Otis TS, et al. (2012). Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue. Nat Commun 3: 1095.