Structure-activity relationships of neuroactive steroids acting on the GABAA receptor
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 actio...
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2009
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paper:paper_09298673_v16_n4_p455_Veleiro2023-06-08T15:52:27Z Structure-activity relationships of neuroactive steroids acting on the GABAA receptor 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 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. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v16_n4_p455_Veleiro http://hdl.handle.net/20.500.12110/paper_09298673_v16_n4_p455_Veleiro |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Structure-activity relationships of neuroactive steroids acting on the GABAA receptor |
| topic_facet |
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 |
| description |
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. |
| title |
Structure-activity relationships of neuroactive steroids acting on the GABAA receptor |
| title_short |
Structure-activity relationships of neuroactive steroids acting on the GABAA receptor |
| title_full |
Structure-activity relationships of neuroactive steroids acting on the GABAA receptor |
| title_fullStr |
Structure-activity relationships of neuroactive steroids acting on the GABAA receptor |
| title_full_unstemmed |
Structure-activity relationships of neuroactive steroids acting on the GABAA receptor |
| title_sort |
structure-activity relationships of neuroactive steroids acting on the gabaa receptor |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v16_n4_p455_Veleiro http://hdl.handle.net/20.500.12110/paper_09298673_v16_n4_p455_Veleiro |
| _version_ |
1768545564459270144 |