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Abstract:

The term "neuroactive steroid" (NAS) refers to steroids which, independent of their origin, are capable of modifying neural activities. These steroids positively or negatively modulate the function of members of the ligand-gated ion channel superfamily. Those with positive allosteric actions on the γ-amino butyric acid type A receptor (GABAA receptor) have been shown to be potent anticonvulsants, anxiolytics, and antistress agents and to possess sedative, hypnotic, and anesthetic activities. New types of neuroactive steroids have been widely sought and structural modifications of the naturally occurring metabolites allopregnanolone, pregnanolone and allotetrahydrodeoxycorticosterone, have been examined in the light of the vast family of GABA receptor subtypes within the brain. Here we review the structure-activity relationship (SAR) of neuroactive steroid analogues obtained by modification of the steroid nucleus, including substitutions at the A, B, C, and D rings and the side chain, with emphasis on the different pharmacophores proposed. © 2009 Bentham Science Publishers Ltd.

Registro:

Documento: Artículo
Título:Structure-activity relationships of neuroactive steroids acting on the GABAA receptor
Autor:Veleiro, A.S.; Burton, G.
Filiación:Departamento de Química Orgánica, UMYMFOR (CONICET-UBA, Universidad de Buenos Aires, Pabellón 2, Buenos Aires, Argentina
Palabras clave:Anticonvulsant; GABAA receptor; Neuroactive steroids; Neurosteroids; Structure-activity relationship; 17 phenyl 5alpha androst 16 en 3alpha ol; 17alpha aza d homosteroid derivative; 17beta alkynyl derivative; 17beta carbonitrile; 2 isopropylmorpholine derivative; 22 bromoalkynyl derivative; 3alpha amino 5alpha pregan 20 one; 3alpha hydroxy 3beta trifluoromethyl 19 nor 5beta pregnan 20 one; 3alpha hydroxy 5alpha pregnan 20 one; 3alpha,21 dihydroxy 5 alpha pregnan 20 one; 3beta carboxamidomethyl; 3beta hydroxymethyl; 3beta methyl derivative; 4 aminobutyric acid receptor; alfaxalone; alkynyl pregnanediol derivative; allotetrahydrodeoxycorticosterone; androsterone; azasteroid derivative; chlorine 36; eltanolone; fluorinated steroid; ganaxolone; minaxolone; oxetane derivative; pregnanediol derivative; steroid; tertiary amine; tetrahydrodeoxycorticosterone; unclassified drug; unindexed drug; 4 aminobutyric acid A receptor; steroid; anticonvulsant activity; anxiety disorder; binding affinity; binding site; brain electrophysiology; cerebellum; clinical trial; drug receptor binding; drug synthesis; drug targeting; drug withdrawal; epilepsy; human; insomnia; membrane binding; nonhuman; pharmacophore; protein expression; protein targeting; review; structure activity relation; structure analysis; synaptic membrane; synaptosome; urticaria; animal; chemical structure; chemistry; physiology; Animals; Humans; Molecular Structure; Receptors, GABA-A; Steroids; Structure-Activity Relationship
Año:2009
Volumen:16
Número:4
Página de inicio:455
Página de fin:472
DOI: http://dx.doi.org/10.2174/092986709787315522
Título revista:Current Medicinal Chemistry
Título revista abreviado:Curr. Med. Chem.
ISSN:09298673
CODEN:CMCHE
CAS:3alpha hydroxy 5alpha pregnan 20 one, 516-54-1; alfaxalone, 23930-19-0; androsterone, 53-41-8; chlorine 36, 13981-43-6, 20193-13-9; eltanolone, 128-20-1; ganaxolone, 38398-32-2; minaxolone, 62571-87-3; tetrahydrodeoxycorticosterone, 567-03-3; Receptors, GABA-A; Steroids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v16_n4_p455_Veleiro

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Citas:

---------- APA ----------
Veleiro, A.S. & Burton, G. (2009) . Structure-activity relationships of neuroactive steroids acting on the GABAA receptor. Current Medicinal Chemistry, 16(4), 455-472.
http://dx.doi.org/10.2174/092986709787315522
---------- CHICAGO ----------
Veleiro, A.S., Burton, G. "Structure-activity relationships of neuroactive steroids acting on the GABAA receptor" . Current Medicinal Chemistry 16, no. 4 (2009) : 455-472.
http://dx.doi.org/10.2174/092986709787315522
---------- MLA ----------
Veleiro, A.S., Burton, G. "Structure-activity relationships of neuroactive steroids acting on the GABAA receptor" . Current Medicinal Chemistry, vol. 16, no. 4, 2009, pp. 455-472.
http://dx.doi.org/10.2174/092986709787315522
---------- VANCOUVER ----------
Veleiro, A.S., Burton, G. Structure-activity relationships of neuroactive steroids acting on the GABAA receptor. Curr. Med. Chem. 2009;16(4):455-472.
http://dx.doi.org/10.2174/092986709787315522