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  • Title: Benzodiazepine receptor ligand actions on GABA responses. Beta-carbolines, purines.
    Author: Skerritt JH, Macdonald RL.
    Journal: Eur J Pharmacol; 1984 May 18; 101(1-2):135-41. PubMed ID: 6086358.
    Abstract:
    The effects of several beta-carboline and purine ligands for benzodiazepine receptors were studied upon GABA (4-aminobutyric acid) responses and upon diazepam enhancement of GABA responses, using mouse spinal cord neurons in dissociated cell culture. While the potent convulsant beta-carboline DMCM (methyl-6,7-dimethyoxy-4-ethyl-carboline-3-carboxylate), reduced GABA responses, methyl-carboline-3-carboxylate (beta CCMe) and the corresponding ethyl ester (beta CCEt) did not alter GABA responses. The propyl ester (beta CCPr) enhanced GABA responses in a concentration-dependent fashion, while both beta CCMe and beta CCPr blocked diazepam enhancement of GABA responses. beta CCPr may thus have partial agonist activity. Two purines with moderate benzodiazepine receptor affinity, 1-methylisoguanosine (MeIG) and 6-dimethylaminopurine (DMAP), weakly enhanced GABA responses. MeIG also significantly antagonized diazepam enhancement of GABA responses. Inosine and hypoxanthine had no apparent actions upon GABA responses or upon diazepam enhancement of such responses. The results with beta-carbolines are consistent with their behavioural profile in vivo and with neurochemical studies of their effects upon GABA-benzodiazepine receptor complexes. Furthermore, certain purines are also able to interact with these complexes.
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