Effects of calcium hopantenate on neurotransmitter receptors in the rat brain

Effects of calcium hopantenate (HOPA) on neurotransmitter and neuropeptide receptors in the central nervous system (CNS) were investigated. In the radioreceptor assay (RRA), HOPA inhibited the [3H]-gamma-aminobutylic acid (GABA) receptor binding in a dose-dependent manner with a cross-reactive potency of 0.2%. On the other hand, radiolabeled ligand binding to CNS receptors in the benzodiazepine (BDZ)-, muscarinic cholinergic (mACh)-, methionine-enkephalin (ENK)- and thyrotropin releasing hormone (TRH)-RRA systems was not inhibited even by the addition of HOPA up to 100 microM. Repeated injection of HOPA (250 mg/kg/day for 7 consecutive days) increased GABA receptor binding by 53% in the cerebral cortex, while GABA binding in the rest of the forebrain did not change. The increased GABA receptor binding in the cerebral cortex of HOPA treated rats was due to the increased affinity of the binding sites. BDZ-, mACh-, ENK- and TRH-receptor bindings were not affected in either the cerebral cortex or the rest of the forebrain by repeated injection of HOPA. These results suggest that at least a part of the therapeutic efficacy of HOPA is due to sensitization of the GABA receptor in the cerebral cortex.