H. Braunerosborne et al., MOLECULAR PHARMACOLOGY OF HOMOLOGS OF IBOTENIC ACID AT CLONED METABOTROPIC GLUTAMIC-ACID RECEPTORS, European journal of pharmacology, 350(2-3), 1998, pp. 311-316
We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxy
isoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues s
ubstituted with a methyl, bromo or butyl group in the four position of
the ring at cloned metabotropic glutamate (mGlu) receptors expressed
in Chinese hamster ovary (CHO) cells. In contrast to the parent compou
nd ibotenic acid, which is a potent group I and II agonist, the (S)-fo
rms of homoibotenic acid and its analogues are selective and potent gr
oup I antagonists whereas the (R)-forms are inactive both as agonists
and antagonists at group I, II, and III mGlu receptors. Interestingly,
(S)-homoibotenic acid and the analogues display equal potency at both
mGlu(1 alpha) and mGlu(5a) with K-i values in the range of 97 to 490
mu M, (S)-homoibotenic acid and (S)-2-amino-3-(4-butyl-3-hydroxyisoxaz
ol acid [(S)-4-butylhomoibotenic acid] displaying the lowest and highe
st potency, respectively. The homoibotenic acid analogues thereby diff
er from mGlu receptor antagonists derived from phenylglycine such as (
S)-4-carboxyphenylglycine which only antagonizes mGlu(1 alpha) (K-i =
18 mu M) showing no effect at mGlu(5a) (K-i > 300 mu M). (C) 1998 Else
vier Science B.V. All rights reserved.