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(+)‐Hydrastine, a potent competitive antagonist at mammalian GABA A receptors
Author(s) -
Huang JunHua,
Johnston Graham A.R.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12997.x
Subject(s) - bicuculline , gabaa receptor , pharmacology , gaba receptor antagonist , muscimol , chemistry , antagonist , competitive antagonist , receptor , biochemistry , biology
1 (+)‐Hydrastine is a phthalide isoquinoline alkaloid, isolated from Corydalis stricta . It has the same 1 S ,9 R configuration as the competitive GABA A receptor antagonist bicuculline and is the enantiomer of the commercially available (−)‐hydrastine. 2 (+)‐Hydrastine (CD 50 0.16 mg kg −1 , i.v.) was twice as potent as bicuculline (CD 50 0.32 mg kg −1 , i.v.) as a convulsant in mice. This action was stereoselective in that (+)‐hydrastine was 180 times as potent as (−)‐hydrastine. 3 (+)‐Hydrastine was a selective antagonist at bicuculline‐sensitive GABA A receptors in the guinea‐pig isolated ileum. It did not influence phaclofen‐sensitive GABA B receptors or acetylcholine receptors in this tissue. (+)‐Hydrastine was a competitive antagonist of GABA A responses (pA 2 6.5) more potent than bicuculline (pA 2 6.1). 4 When tested against the binding of [ 3 H]‐muscimol to high affinity GABA A binding sites in rat brain membranes, (+)‐hydrastine (IC 50 2.37 μ m ) was 8 times more potent than bicuculline (IC 50 19.7 μ m ). 5 As an antagonist of the activation of low affinity GABA A receptors as measured by the stimulation by GABA of [ 3 H]‐diazepam binding to rat brain membranes, (+)‐hydrastine (IC 50 0.4 μ m ) was more potent than bicuculline (IC 50 2.3 μ m ). 6 (+)‐Hydrastine, 10 n m to 1 m m , did not inhibit the binding of [ 3 H]‐(−)‐baclofen to GABA B binding sites in rat brain membranes.