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mGlu Receptors-Briston(3)

时间:2005-11-15 19:00来源:www.bris.ac.uk 作者:bioguider 点击: 951次
>1000
-
>200
>100
mGlu 3
>1000
-
>200
>100
   
Group III
mGlu 4
0.9
1.0
5.2
8.8 ± 1.1
mGlu 6
0.6
0.4
4.7
3.6 ± 0.8
mGlu 7
252
31
185
>100
mGlu 8
0.06-0.6
0.3
0.2
0.031 ± 0.002
 

 

mGlu Receptor Antagonists

This section will describe the most useful antagonists for the mGlu receptors, indicating which compounds display subtype selectivity. Antagonist pharmacology of the mGlu receptors is complex, with some compounds acting as an antagonist at one receptor subtype but an agonist at another. In addition, some antagonists display agonist-dependent antagonism i.e the potency of an antagonist is dependent on the agonist used to elicit the functional response to be inhibited. This phenomenon is particularly noticable with group I mGlu receptor antagonists.

Broad spectrum mGlu Receptor Antagonists These compounds act at more than one group of mGlu receptors, and includes the most commonly used mGlu receptor antagonist, (S)-MCPG, a compound developed in Bristol. (S)-MCPG is a competitive antagonist of both group I and group II receptors, showing a degree of selectivity for mGlu1 over mGlu5 receptors within group I. There is some evidence that (S)-MCPG may display agonist-dependent antagonism at mGlu5 receptors, inhibiting (1S,3R)-ACPD-evoked but not L-glutamate-evoked phosphoinositide turnover. However, no difference has been detected in the ability of (S)-MCPG to block either L-glutamate- or (S)-DHPG-evoked calcium release. LY341495 and it's structurally related epimer, the recently reported LY344545 are two other compounds that, when used at high concentrations, are broad spectrum antagonists. However, at lower concentrations, these two compounds show different pharmalogical profiles. LY341495 is an extremely potent antagonist of group II mGlu receptors. Interestingly, some effects of (S)-MCPG are not reproduced by LY341495 suggesting that there may be more mGlu receptors that have yet to be cloned. Although for most mGlu receptors, LY344545 has a lower affinity, potency at mGlu5 receptors is slightly raised. Thus, importantly, LY344545 is a selective, competitive antagonist of mGlu5 receptors, within group I.

 

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(S)-MCPG
LY341495
LY344545
   
IC 50 Values (µM)
Group I
mGlu 1
50 - 500
6.8
39.5
mGlu 5
300 - >2000
8.2
5.5
   
Group II
mGlu 2
50 - 150
0.021
9.5
mGlu 3
317
0.014
10.7
   
Group III
mGlu 4
>1000
22
>100
mGlu 6
>100
-
64.8
mGlu 7
顶一下
(44)
100%
踩一下
(0)
0%
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