Affinity of the mGlu2/3 agonists LY354740, LY379268 and the mGlu2/3 antagonist LY341495 at both cloned human (h) metabotropic glutamate receptors (binding studies and functional assays) and rat forebrain homogenates compared with functional effects on 5-HT-induced EPSCs and early and late components of the electrically evoked EPSPs following DOI treatment.
| Mean ± S.E. (nM) | |||
|---|---|---|---|
| LY354740 | LY379268 | LY341495 | |
| Inhibition of forskolin-activated adenylyl cyclase | |||
| Human mGlu2 (EC50) | 5.1 ± 0.33-a | 2.7 ± 0.33-a | |
| Human mGlu3 (EC50) | 24.3 ± 0.53-a | 4.6 ± 0.13-a | |
| 5-HT-induced EPSCs and evoked EPSPs | |||
| 5-HT-induced EPSCsb | 89 ± 30 (EC50) | 231 ± 54 (EC50) | 54 ± 7.0 (K b) |
| Evoked late EPSPs after DOIc | 85 ± 22 (EC50) | 260 ± 151 (EC50) | N.D. |
| Evoked early EPSPsd | 235 ± 108 (EC50) | 276 ± 84 (EC50) | 13 ± 6.7 (K b) |
N.D., not determined.
↵3-a Potency (EC50, nM) for suppression of forskolin-activated adenylyl cyclase for LY35740 (Schoepp et al., 1997) and LY379268 (Monn et al., 1999).
b,c,d EC50 values (nM) for agonists at suppressing 5-HT-induced EPSCs, evoked late EPSCs after DOI, and evoked early EPSPs. “Apparent” Kb value of antagonist for blocking suppressant action of LY354740 (nM) as determined from pA2 value.