(±)-trans-ACPD

(±)-trans-ACPD is an agonist of metabotropic glutamate receptors (mGluRs; EC₅₀s = 15, 2, 40, 23, and 82 µM for mGluR1, -2, -3, -5, and -6, respectively, in CHO cells expressing recombinant receptors).¹ It also activates mGluR4 in baby hamster kidney cells with an EC₅₀ value of approximately 800 µM. (±)-trans-ACPD increases cAMP accumulation in adult rat cerebral cortex slices (EC₅₀ = 47.8 µM) but not in isolated rat embryonic neurons or neonatal glial cells when used at concentrations ranging from 1 to 1,000 µM.² (±)-trans-ACPD (10-1,000 µM) increases phosphoinositide hydrolysis in neonatal rat cerebral cortex and hippocampal slices. It induces clonic convulsions in neonatal rats (ED₅₀ = 100 mg/kg), an effect that can be reversed by administration of the NMDA receptor antagonists LY233053 and LY274614.³

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1. Kozikowski, A.P., Steensma, D., Araldi, G.L., et al. Synthesis and biology of the conformationally restricted ACPD analogue, 2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I, a potent mGluR agonist. J. Med. Chem. 41(10), 1641-1650 (1998).

2. Pilc, A., Legutko, B., Frankiewicz, T., et al. Trans-(+-)-1-amino-1,3-cyclopentanedicarboxylate (trans-ACPD) stimulates cAMP accumulation in rat cerebral cortical slices but not in glial or neuronal cultures. Neurosci. Lett. 169(1-2), 171-174 (1994).

3. Schoepp, D.D., Johnson, B.G., Salhoff, C.R., et al. In vitro and in vivo pharmacology of trans- and cis-(+-)-1-amino-1,3-cyclopentanedicarboxylic acid: Dissociation of metabotropic and ionotropic excitatory amino acid receptor effects. J. Neurochem. 56(5), 1789-1796 (1991).