Abstract
In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-homo-ACPD) and the racemic mixture of (1RS,2RS)-1-amino-1-carboxycyclopentane-2-acetic acid (1RS,2RS-homo-ACPD), (1RS,2RS)-Homo-ACPD was shown to be a competitive mGlu2 receptor antagonist with a KB of 391 microM. (1S,3R)-Homo-ACPD and (1R,3R)-homo-ACPD were both shown to be mGlu2 receptor agonists with EC50 values of 122 and 105 microM, respectively. Compared to (S)-Glu both compounds displayed partial agonism with intrinsic activities of 79% and 47%, respectively. (1S,3S)-Homo-ACPD was also found to be a partial mGlu2 receptor agonist with an intrinsic activity of 27% compared to (S)-Glu. None of the compounds tested showed any activity at mGlu1a or mGlu4a receptors. These homo-ACPD's show a higher degree of subtype selectivity than the parent compound (1SR,3RS)-ACPD. In addition none of the compounds demonstrated any activity at ionotropic Glu receptors.
| Original language | English |
|---|---|
| Journal | European Journal of Pharmacology |
| Volume | 332 |
| Issue number | 3 |
| Pages (from-to) | 327-31 |
| Number of pages | 5 |
| ISSN | 0014-2999 |
| Publication status | Published - 13 Aug 1997 |
Keywords
- Animals
- CHO Cells
- Cricetinae
- Cycloleucine
- Glutamic Acid
- Receptors, Metabotropic Glutamate
- Second Messenger Systems
- Stereoisomerism
- Structure-Activity Relationship