A substituted anilino enaminone acts as a novel positive allosteric modulator of GABAA receptors in the mouse brain

Journal of Pharmacology and Experimental Therapeutics

Volumn 336, Issue 3, 2011, Pages 916-924

  Wang, Ze Jun ^a   Sun, Liqin ^a   Jackson, Patrice L ^c   Scott, Kenneth R ^b   Heinbockel, Thomas ^a  

^a HOWARD UNIVERSITY COLLEGE OF MEDICINE   (United States)

^b HOWARD UNIVERSITY   (United States)

^c UNIVERSITY OF MARYLAND EASTERN SHORE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (BENZHYDRYLIDENEAMINOOXY)ETHYL] 1,2,5,6 TETRAHYDRO 3 PYRIDINECARBOXYLIC ACID; 1 [2 [TRIS(4 METHOXYPHENYL)METHOXY]ETHYL]3 PIPERIDINECARBOXYLIC ACID; 1 [2 [TRIS(4 METHOXYPHENYL)METHYL]ETHYL] 3 PIPERIDINECARBOXYLIC ACID; 2 AMINO 5 PHOSPHONOVALERIC ACID; 3 (3 CHLOROPHENYLAMINO) 5 METHYLCYCLOHEX 2 ENONE; 3 (4 FLUOROPHENYLAMINO) 5 METHYLCYCLOHEX 2 ENONE; 3 AMINO 2 (3 CARBOXYPROPYL) 6 (4 METHOXYPHENYL)PYRIDAZINIUM BROMIDE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR BLOCKING AGENT; 4 AMINOBUTYRIC ACID B RECEPTOR BLOCKING AGENT; 4 CARBO TERT BUTOXY 5 METHYLCYCLOHEXANE 1,3 DIONE; 4 CARBOXY 2 METHYLPHENYLGLYCINE; 5 METHYL 3 (4 TRIFLUOROMETHOXYPHENYLAMINO)CYCLOHEX 2 ENONE; 5 METHYLCYCLOHEXANE 1,3 DIONE; 6 CYANO 7 NITRO 2,3 QUINOXALINEDIONE; ANILINE DERIVATIVE; BENZODIAZEPINE RECEPTOR BLOCKING AGENT; BENZYL[3 [[1 (3,4 DICHLOROPHENYL)ETHYL]AMINO] 2 HYDROXYPROPYL]PHOSPHINIC ACID; ENAMINONE; FLUMAZENIL; PENTETRAZOLE; UNCLASSIFIED DRUG; VIGABATRIN;

4 AMINOBUTYRIC ACID BRAIN LEVEL; ALLOSTERISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; BRAIN SLICE; CELL ACTIVITY; CELL MEMBRANE POTENTIAL; CELL POLARITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CONVULSION; DRUG EFFECT; DRUG ELIMINATION; DRUG PROTEIN BINDING; DRUG UPTAKE; MITRAL CELL; MOUSE; NERVE CELL; NERVE CELL EXCITABILITY; NERVE CELL INHIBITION; NEUROMODULATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OLFACTORY BULB; PATCH CLAMP; PRIORITY JOURNAL; WHOLE CELL;

ACTION POTENTIALS; ALLOSTERIC REGULATION; ANIMALS; ANTICONVULSANTS; BRAIN; GABA MODULATORS; MICE; MICE, INBRED C57BL; PROTEIN BINDING; RECEPTORS, GABA-A;

EID: 79951986050     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.110.173740     Document Type: Article

References (42)

1. Abdel-Hamid ME, Edafiogho IO, and Scott KR (2002) LC/MS determination of the enaminones E139, DM5 and DM27 in rat serum. J Pharm Biomed Anal 30:1001-1011. (Pubitemid 35284312)
2. Ananthalakshmi KV, Edafiogho IO, and Kombian SB (2006) Concentration-dependent effects of anticonvulsant enaminone methyl 4-(4′-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability in vitro. Neuroscience 141:345-356.
3. Ananthalakshmi KV, Edafiogho IO, and Kombian SB (2007) Anticonvulsant enaminone E139 suppresses epileptiform activity in rat hippocampal slices. Epilepsy Res 76:85-92. (Pubitemid 47419281)
4. Bowery NG, Hudson AL, and Price GW (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20:365-383. (Pubitemid 17048701)
5. B receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro. Brain Res Bull 67:310-318.
6. Chu DC, Albin RL, Young AB, and Penney JB (1990) Distribution and kinetics of GABAB binding sites in rat central nervous system: a quantitative autoradiographic study. Neuroscience 34:341-357. (Pubitemid 20110140)
7. Edafiogho IO, Ananthalakshmi KV, and Kombian SB (2006) Anticonvulsant evaluation and mechanism of action of benzylamino enaminones. Bioorg Med Chem 14:5266-5272. (Pubitemid 43903256)
8. Edafiogho IO, Hinko CN, Chang H, Moore JA, Mulzac D, Nicholson JM, and Scott KR (1992) Synthesis and anticonvulsant activity of enaminones. J Med Chem 35:2798-2805.
9. Edafiogho IO, Kombian SB, Ananthalakshmi KV, Salama NN, Eddington ND, Wilson TL, Alexander MS, Jackson PL, Hanson CD, and Scott KR (2007) Enaminones: exploring additional therapeutic activities. J Pharm Sci 96:2509-2531. (Pubitemid 47597808)
10. Edafiogho IO, Phillips OA, Udo EE, Samuel S, and Rethish B (2009) Synthesis, antibacterial and anticonvulsant evaluations of some cyclic enaminones. Eur J Med Chem 44:967-975.
11. Eddington ND, Cox DS, Khurana M, Salama NN, Stables JP, Harrison SJ, Negussie A, Taylor RS, Tran UQ, Moore JA, et al. (2003) Synthesis and anticonvulsant activity of enaminones. Part 7. Synthesis and anticonvulsant evaluation of ethyl 4-[(substituted phenyl)amino]-6-methyl-2-oxocyclohex-3-ene- 1-carboxylates and their corresponding 5-methylcyclohex-2-enone derivatives. Eur J Med Chem 38: 49-64. (Pubitemid 36197854)
12. Eddington ND, Cox DS, Roberts RR, Stables JP, Powell CB, and Scott KR (2000) Enaminones-versatile therapeutic pharmacophores. Further advances. Curr Med Chem 7:417-436. (Pubitemid 30396434)
13. Ennis M, Hamilton KA, Hayar A (2007) Neurochemistry of the main olfactory system, in Handbook of Neurochemistry and Molecular Neurobiology (Lajtha A, ed), Sensory Neurochemistry (Johnson DA, volume ed), 3rd ed, vol 20, pp 137-204, Springer, Heidelberg, Germany.
14. Errante LD, Williamson A, Spencer DD, and Petroff OA (2002) Gabapentin and vigabatrin increase GABA in the human neocortical slice. Epilepsy Res 49:203-210. (Pubitemid 34655561)
15. Fisher JL (2009) The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator. Neuropharmacology 56:190-197.
16. Foster JE, Nicholson JM, Butcher R, Stables JP, Edafiogho IO, Goodwin AM, Henson MC, Smith CA, and Scott KR (1999) Synthesis, characterization and anticonvulsant activity of enaminones. Part 6: Synthesis of substituted vinylic benzamides as potential anticonvulsants. Bioorg Med Chem 7:2415-2425.
17. Friary RJ, Gilligan JM, Szajewski RP, Falci KJ, and Franck RW (1973) Heterocyclic synthesis via the intramolecular acylation of enamines derived from amino acids. J Org Chem 38:3487-3491.
18. Heinbockel T, Heyward P, Conquet F, and Ennis M (2004) Regulation of main olfactory bulb mitral cell excitability by metabotropic glutamate receptor mGluR1. J Neurophysiol 92:3085-3096. (Pubitemid 40340514)
19. Heyward P, Ennis M, Keller A, and Shipley MT (2001) Membrane bistability in olfactory bulb mitral cells. J Neurosci 21:5311-5320. (Pubitemid 32622957)
20. A receptor modulators. J Med Chem 50:3369-3379.
21. Isaacson JS and Vitten H (2003) GABA(B) receptors inhibit dendrodendritic transmission in the rat olfactory bulb. J Neurosci 23:2032-2039. (Pubitemid 36368890)
22. Jackson PL, Scott KR, Southerland WM, and Fang YY (2009) Enaminones 8: CoMFA and CoMSIA studies on some anticonvulsant enaminones. Bioorg Med Chem 17:133-140.
23. Kombian SB, Edafiogho IO, and Ananthalakshmi KV (2005) Anticonvulsant enaminones depress excitatory synaptic transmission in the rat brain by enhancing extracellular GABA levels. Br J Pharmacol 145:945-953. (Pubitemid 41129016)
24. Laurie DJ, Seeburg PH, and Wisden W (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. J Neurosci 12:1063-1076.
25. McNamara JO (1996) Drugs effective in the therapy of the epilepsies, in The Pharmacological Basis of Therapeutics (Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, and Gilman AG eds), pp 461-486, McGraw-Hill, New York.
26. Möhler H, Fritschy JM, and Rudolph U (2002) A new benzodiazepine pharmacology. J Pharmacol Exp Ther 300:2-8. (Pubitemid 34028501)
27. Mulzac D and Scott KR (1993) Profile of anticonvulsant activity and minimal toxicity of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3- en-1-oate and some prototype antiepileptic drugs in mice and rats. Epilepsia 34:1141-1146.
28. Munro G, Lopez-Garcia JA, Rivera-Arconada I, Erichsen HK, Nielsen EØ, Larsen JS, Ahring PK, and Mirza NR (2008) Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3′-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2- carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 327:969-981.
29. Palouzier-Paulignan B, Duchamp-Viret P, Hardy AB, and Duchamp A (2002) GABA(B) receptor-mediated inhibition of mitral/tufted cell activity in the rat olfactory bulb: a whole-cell patch-clamp study in vitro. Neuroscience 111:241-250. (Pubitemid 34442610)
30. Panzanelli P, Perazzini AZ, Fritschy JM, and Sassoè-Pognetto M (2005) Heterogeneity of γ-aminobutyric acid type A receptors in mitral and tufted cells of the rat main olfactory bulb. J Comp Neurol 484:121-131.
31. Persohn E, Malherbe P, and Richards JG (1992) Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS. J Comp Neurol 326:193-216.
32. Rall TW and Schleifer LS (1990) Drugs effective in the therapy of the epilepsies, in The Pharmacological Basis of Therapeutics (Goodman AG, Rall TW, Nies AS, and Taylor P eds) pp 436-462, Pergamon Press, New York.
33. Reitz AB, Fitzpatrick LJ, Jordan AD, and Sanfilippo PJ (1999) inventors; Ortho Pharmaceutical Corporation, assignee. 5-[(Heteroaryl)alkyl]-3-oxo- pyrido[1,2-a]benzimidazole-4-carboxamide derivatives useful in treating central nervous system disorders. US patent: 5,922,731. 1999 July 13.
34. Rho JM and Sankar R (1999) The pharmacologic basis of antiepileptic drug action. Epilepsia 40:1471-1483. (Pubitemid 29518074)
35. Santhakumar V, Wallner M, and Otis TS (2007) Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition. Alcohol 41:211-221. (Pubitemid 46970812)
36. Scott KR, Edafiogho IO, Richardson EL, Farrar VA, Moore JA, Tietz EI, Hinko CN, Chang H, el-Assadi A, and Nicholson JM (1993) Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations. J Med Chem 36:1947-1955.
37. Shepherd GW, Chen WR, and Greer CA (2004) Olfactory bulb, in The Synaptic Organization of the Brain (Shepherd GM ed) pp 165-216, Oxford, New York.
38. Snell LD, Claffey DJ, Ruth JA, Valenzuela CF, Cardoso R, Wang Z, Levinson SR, Sather WA, Williamson AV, Ingersoll NC, et al. (2000) Novel structure having antagonist actions at both the glycine site of the N-methyl-D-aspartate receptor and neuronal voltage-sensitive sodium channels: biochemical, electrophysiological, and behavioral characterization. J Pharmacol Exp Ther 292:215-227. (Pubitemid 30026374)
39. Stables JP and Kupferberg HJ (1997) The NIH Anticonvulsant Drug Development (ADD) Program: preclinical anticonvulsant screening project, in Molecular and Cellular Targets for Anti-epileptic Drugs (Avanzini G, Regesta G, Tanganelli P, and Avoli M eds), pp 191-198, John Libbey & Company Ltd, London.
40. Traynelis SF and Dingledine R (1988) Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. J Neurophysiol 59:259-276. (Pubitemid 18038311)
41. Wang ZJ, Snell LD, Tabakoff B, and Levinson SR (2002) Inhibition of neuronal Na+ channels by the novel antiepileptic compound DCUKA: identification of the diphenylureido moiety as an inactivation modifier. Exp Neurol 178:129-138. (Pubitemid 35425616)
42. Yohannes D, Maynard G, Yuan J, Xie L, Lee K, Ghosh M, Luke G, Liu X, Nagal A, Vincent L, et al. (2003) inventors; Neurogen Corporation, assignee. Heterocyclic compounds as ligands of the GABAA receptor. U.S. patent 6,653,471. 2003 Nov 25.