Anticonvulsant profile of the neuroactive steroid, SGE-516, in animal models

Epilepsy Research

Volumn 134, Issue , 2017, Pages 16-25

  Hammond, Rebecca S ^a   Althaus, Alison L ^a   Ackley, Michael A ^a   Maciag, Carla ^a   Martinez Botella, Gabriel ^a   Salituro, Francesco G ^a   Robichaud, Albert J ^a   Doherty, James J ^a  

^a Sage Therapeutics Inc   (United States)

Author keywords

Allopregnanolone; Convulsion; GABAA receptor; Neuroactive steroids; Pentylenetetrazol (PTZ); Seizure

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ANTICONVULSIVE AGENT; BREXANOLONE; SGE 516; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID; 4-AMINOPIPERIDINE; CONVULSANT AGENT; ELTANOLONE; FMR1 PROTEIN, MOUSE; FRAGILE X MENTAL RETARDATION PROTEIN; PENTETRAZOLE; PIPERIDINE DERIVATIVE; POTASSIUM CHANNEL BLOCKING AGENT;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; EPILEPTIC DISCHARGE; FIRING RATE; HIPPOCAMPAL SLICE; IN VITRO STUDY; IN VIVO STUDY; KINDLING; MALE; MOUSE; NERVE CELL; NERVE CELL NETWORK; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; RAT; SEIZURE; TEMPORAL LOBE EPILEPSY; WHOLE CELL PATCH CLAMP; ACTION POTENTIAL; ANIMAL; CYTOLOGY; DISEASE MODEL; DRUG EFFECTS; ELECTRIC SHOCK; GENETICS; HIPPOCAMPUS; KNOCKOUT MOUSE; METABOLISM; SPRAGUE DAWLEY RAT;

ACTION POTENTIALS; ANIMALS; ANTICONVULSANTS; CONVULSANTS; DISEASE MODELS, ANIMAL; ELECTROSHOCK; FRAGILE X MENTAL RETARDATION PROTEIN; GAMMA-AMINOBUTYRIC ACID; HIPPOCAMPUS; KINDLING, NEUROLOGIC; MALE; MICE; MICE, KNOCKOUT; PENTYLENETETRAZOLE; PIPERIDINES; POTASSIUM CHANNEL BLOCKERS; PREGNANOLONE; RATS; RATS, SPRAGUE-DAWLEY; SEIZURES;

EID: 85019200404     PISSN: 09201211     EISSN: 18726844     Source Type: Journal    
DOI: 10.1016/j.eplepsyres.2017.05.001     Document Type: Article

References (49)

1. Ahring, P.K., Bang, L.H., Jensen, M.L., Strobaek, D., Hartiadi, L.Y., Chebib, M., Absalom, N., A pharmacological assessment of agonists and modulators ata4b2g2 anda4b2d GABAA receptors: the challenge in comparing apples with oranges. Pharmacol. Res. 111 (2016), 563–576, 10.1016/j.phrs.2016.05.014.
2. Amin, J., Brooks-Kayal, A., Weiss, D., Two tyrosine residues on the α subunit are crucial for benzodiazepine binding and allosteric modulation of γ-aminobutyric acidA receptors. Mol. Pharmacol. 841 (1997), 833–841.
3. Avoli, M., Jefferys, J.G.R., Models of drug-induced epileptiform synchronization in vitro. J. Neurosci. Methods 260 (2015), 26–32, 10.1016/j.jneumeth.2015.10.006.
4. Belelli, D., Lambert, J.J., Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat. Rev. Neurosci. 6 (2005), 565–575, 10.1038/nrn1703.
5. Belelli, D., Bolger, M.B., Gee, K.W., Anticonvulsant profile of the progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one. Eur. J. Pharmacol. 166 (1989), 325–329, 10.1016/0014-2999(89)90077-0.
6. Belelli, D., Casula, A., Ling, A., Lambert, J., The influence of subunit composition on the interaction of neurosteroids with GABA A receptors. Neuropharmacology 43 (2002), 651–661.
7. Belelli, D., Harrison, N.L., Maguire, J., Macdonald, R.L., Walker, M.C., Cope, D.W., Extrasynaptic GABAA receptors: form, pharmacology, and function. J. Neurosci. 29 (2009), 12757–12763, 10.1523/JNEUROSCI.3340-09.2009.
8. Calcaterra, N.E., Barrow, J.C., Classics in chemical neuroscience: diazepam (Valium). ACS Chem. Neurosci. 5 (2014), 253–260.
9. Carter, R.B., Wood, P.L., Wieland, S., Hawkinson, J.E., Belelli, D., Lambert, J.J., White, H.S., Wolf, H.H., Mirsadeghi, S., Tahir, S.H., Bolger, M.B., Lan, N.C., Gee, K.W., Characterization of the anticonvulsant properties of ganaxolone (CCD 1042; 3α-hydroxy-3α-methyl-5α-pregnan-20-one), a selective, high-affinity, steroid modulator of the γ-aminobutyric AcidA receptor. J. Pharmacol. Exp. Ther. 280 (1997), 1284–1295.
10. Deeb, T.Z., Maguire, J., Moss, S.J., Possible alterations in GABAA receptor signaling that underlie benzodiazepine-resistant seizures. Epilepsia 53 (2012), 79–88.
11. Farrant, M., Nusser, Z., Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat. Rev. Neurosci. 6 (2005), 215–229, 10.1038/nrn1625.
12. Goodkin, H.P., Joshi, S., Mtchedlishvili, Z., Brar, J., Kapur, J., Subunit-specific trafficking of GABA(A) receptors during status epilepticus. J. Neurosci. 28 (2008), 2527–2538, 10.1523/JNEUROSCI.3426-07.2008.
13. Gramowski-Voß, A., Schwertle, H.-J., Pielka, A.-M., Schultz, L., Steder, A., Jügelt, K., Axmann, J., Pries, W., Enhancement of cortical network activity in vitro and promotion of GABAergic neurogenesis by stimulation with an electromagnetic field with a 150 MHz carrier wave pulsed with an alternating 10 and 16 Hz modulation. Front. Neurol., 6, 2015, 158, 10.3389/fneur.2015.00158.
14. Gravielle, M.C., Activation-induced regulation of GABAA receptors: is there a link with the molecular basis of benzodiazepine tolerance?. Pharmacol. Res., 2015, 1–9, 10.1016/j.phrs.2015.12.030.
15. Hammer, H., Bader, B.M., Ehnert, C., Bundgaard, C., Bunch, L., Hoestgaard-Jensen, K., Schroeder, O.H.-U., Bastlund, J.F., Gramowski-Voß, A., Jensen, A.A., A multifaceted GABAA receptor modulator: functional properties and mechanism of action of the sedative-hypnotic and recreational drug methaqualone (Quaalude). Mol. Pharmacol. 88 (2015), 401–420, 10.1124/mol.115.099291.
16. Heulens, I., D'Hulst, C., Van Dam, D., De Deyn, P.P., Kooy, R.F., Pharmacological treatment of fragile X syndrome with GABAergic drugs in a knockout mouse model. Behav. Brain Res. 229 (2012), 244–249, 10.1016/j.bbr.2012.01.031.
17. Hosie, A.M., Wilkins, M.E., Smart, T.G., Neurosteroid binding sites on GABA(A) receptors. Pharmacol. Ther. 116 (2007), 7–19, 10.1016/j.pharmthera.2007.03.011.
18. Jacob, T.C., Michels, G., Silayeva, L., Haydon, J., Succol, F., Moss, S.J., Benzodiazepine treatment induces subtype-specific changes in GABA(A) receptor trafficking and decreases synaptic inhibition. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 18595–18600, 10.1073/pnas.1204994109.
19. Kaminski, R.M., Livingood, M.R., Rogawski, M.A., Allopregnanolone analogs that positively modulate GABAA receptors protect against partial seizures induced by 6-Hz electrical stimulation in mice. Epilepsia 45 (2004), 864–867, 10.1111/j.0013-9580.2004.04504.x.
20. Kanes, S., Rosenthal, E., Vaitkevicius, H., Claassen, J., Wainwright, M., Hoffmann, E., Baird, M., Quirk, M., Colquhoun, H., SAGE–547 for the treatment of super-refractory status epilepticus: response and relationship to underlying patient characteristics. Neurocrit. Care, 2016 p. 25:S205.
21. Kokate, T.G., Svensson, B.E., Rogawski, M.A., Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J. Pharmacol. Exp. Ther. 270 (1994), 1223–1229.
22. Kokate, T.G., Cohen, a L., Karp, E., Rogawski, M.A., Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice. Neuropharmacology 35 (1996), 1049–1056.
23. Kupferberg, H., Animal models used in the screening of antiepileptic drugs. Epilepsia 42 (2008), 7–12, 10.1111/j.1528-1167.2001.00002.x.
24. Lee, V., Maguire, J., The impact of tonic GABAA receptor-mediated inhibition on neuronal excitability varies across brain region and cell type. Front. Neural Circuits, 8, 2014, 3, 10.3389/fncir.2014.00003.
25. Li Zhang, C., Dreier, J.P., Heinemann, U., Paroxysmal epileptiform discharges in temporal lobe slices after prolonged exposure to low magnesium are resistant to clinically used anticonvulsants. Epilepsy Res. 20 (1995), 105–111, 10.1016/0920-1211(94)00067-7.
26. Lonsdale, D., Burnham, W.M., The anticonvulsant effects of allopregnanolone against amygdala-kindled seizures in female rats. Neurosci. Lett. 411 (2007), 147–151, 10.1016/j.neulet.2006.10.023.
27. Magiorkinis, E., Diamantis, A., Sidiropoulou, K., Panteliadis, C., Highights in the history of epilepsy: the last 200 years. Epilepsy Res. Treat., 2014, 582039, 10.1155/2014/582039.
28. Martin, B.S., Martinez-Botella, G., Loya, C.M., Salituro, F.G., Robichaud, A.J., Huntsman, M.M., Ackley, M.A., Doherty, J.J., Corbin, J.G., Rescue of deficient amygdala tonic γ-aminobutyric acidergic currents in the Fmr-/y mouse model of fragile X syndrome by a novel γ-aminobutyric acid type A receptor-positive allosteric modulator. J. Neurosci. Res. 94 (2016), 568–578, 10.1002/jnr.23632.
29. A receptor: structure-activity relationships of heterocyclic substitution at C-21. J. Med. Chem. 58 (2015), 3500–3511, 10.1021/acs.jmedchem.5b00032.
30. Martinez-Botella, G., Ackley, M.A., Salituro, F.G., Natural and synthetic neuroactive steroid modulators of GABA a and NMDA receptors. Annu. Rep. Med. Chem. 49 (2014), 27–42.
31. Modgil, A., Parakala, M.L., Ackley, M.A., Doherty, J.J., Moss, S.J., Davies, P.A., Endogenous and synthetic neuroactive steroids evoke sustained increases in the efficacy of GABAergic inhibition via a protein kinase C-dependent mechanism. Neuropharmacology 113 (2017), 314–322, 10.1016/j.neuropharm.2016.10.010.
32. Naylor, D.E., Liu, H., Wasterlain, C.G., Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J. Neurosci. 25 (2005), 7724–7733, 10.1523/JNEUROSCI.4944-04.2005.
33. Naylor, D.E., Trafficking of GABAA receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J. Neurosci. 25 (2005), 7724–7733, 10.1523/JNEUROSCI.4944-04.2005.
34. Olmos-Serrano, J.L., Paluszkiewicz, S.M., Martin, B.S., Kaufmann, W.E., Corbin, J.G., Huntsman, M.M., Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome. J. Neurosci. 30 (2010), 9929–9938, 10.1523/JNEUROSCI.1714-10.2010.
35. Paluszkiewicz, S.M., Martin, B.S., Huntsman, M.M., Fragile X syndrome: the GABAergic system and circuit dysfunction. Dev. Neurosci. 33 (2011), 349–364, 10.1159/000329420.
36. Puia, G., Gullo, F., Dossi, E., Lecchi, M., Wanke, E., Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array recording study. Front. Neural Circuits, 6, 2012, 94, 10.3389/fncir.2012.00094.
37. Racine, R.J., Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr. Clin. Neurophysiol. 32 (1972), 281–294.
38. Reddy, D.S., Estes, W.A., Clinical potential of neurosteroids for CNS disorders. Trends Pharmacol. Sci. 37 (2016), 543–561, 10.1016/j.tips.2016.04.003.
39. Rogawski, M.A., Loya, C.M., Reddy, K., Zolkowska, D., Lossin, C., Neuroactive steroids for the treatment of status epilepticus. Epilepsia 54:Suppl. 6 (2013), 93–98, 10.1111/epi.12289.
40. Rowley, N.M., White, H.S., Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: correlation with other seizure and epilepsy models. Epilepsy Res. 92 (2010), 163–169, 10.1016/j.eplepsyres.2010.09.002.
41. Salazar, P., Tapia, R., Rogawski, M. a., Effects of neurosteroids on epileptiform activity induced by picrotoxin and 4-aminopyridine in the rat hippocampal slice. Epilepsy Res. 55 (2003), 71–82, 10.1016/S0920-1211(03)00112-8.
42. Sigel, E., Steinmann, M.E., Structure, function, and modulation of GABAA receptors. J. Biol. Chem. 287 (2012), 40224–40231, 10.1074/jbc.R112.386664.
43. Staley, K., Molecular mechanisms of epilepsy. Nat. Neurosci. 18 (2015), 367–372, 10.1038/nn.3947.
44. Tellez-Zenteno, J.F., Hernandez-Ronquillo, L., Buckley, S., Zahagun, R., Rizvi, S., A validation of the new definition of drug-resistant epilepsy by the International League Against Epilepsy. Epilepsia 55 (2014), 829–834.
45. Treiman, D.M., GABAergic mechanisms in epilepsy. Epilepsia 42:Suppl. 3 (2001), 8–12.
46. Wafford, K.A., Macaulay, A.J., Fradley, R., O'Meara, G.F., Reynolds, D.S., Rosahl, T.W., Differentiating the role of gamma-aminobutyric acid type A (GABAA) receptor subtypes. Biochem. Soc. Trans. 32 (2004), 553–556, 10.1042/BST0320553.
47. Wieland, H.A., Lüddens, H., Seeburg, P.H., A single histidine in GABAA receptors is essential for benzodiazepine agonist binding. J. Biol. Chem. 267 (1992), 1426–1429 VL – 267.
48. Wieland, S., Belluzzi, J.D., Stein, L., Lan, N.C., Comparative behavioral characterization of the neuroactive steroids 3 alpha-OH,5 alpha-pregnan-20-one and 3 alpha-OH,5 beta-pregnan-20-one in rodents. Psychopharmacology (Berl) 118 (1995), 65–71.
49. Zorumski, C.F., Mennerick, S., Neurosteroids as therapeutic leads in psychiatry. JAMA Psychiatry 63110 (2013), 1–2, 10.1001/jamapsychiatry.2013.245.