The interaction of benzodiazepine (BZ) and beta carbolines with GABAA receptor-gated chloride channels using 36Cl influx biochemical functional assay in mammalian spinal cord cultured neurons was investigated. BZ-receptor agonists such as flunitrazepam, diazepam, clonazepam and flurazepam enhanced the effect of submaximal concentrations of GABA (10 microM)-stimulated 36Cl influx. The rank order of potencies was flunitrazepam greater than clonazepam greater than diazepam greater than flurazepam. In contrast, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), ethyl-beta-carboline-3-carboxylate (beta-CCE), N-methyl-beta-carboline-3-carboxamide (FG 7142) and ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5 alpha][1,4]-benzodiazepine-3-carboxylate (Ro 15-4513) inhibited GABA-stimulated 36Cl influx. The rank order of inhibitory potencies for the inverse agonists was DMCM greater than beta-CCE greater than Ro 15-4513 greater than FG 7142. Although lower concentrations of Ro 15-1788 antagonized the enhancement of BZ agonists like diazepam and the inhibition of inverse agonists like DMCM on GABA-stimulated 36Cl influx without exhibiting any effect per se, higher concentrations of Ro 15-1788 (greater than or equal to 10(-6) M) enhanced GABA-stimulated 36Cl influx. These observations indicate that flunitrazepam, diazepam, clonazepam and flurazepam are agonists; DMCM, beta-CCE, Ro 15-4513 and FG 7142 are inverse agonists, whereas Ro 15-1788 is antagonist at lower concentrations and partial agonist at higher concentrations at the BZ receptors.(ABSTRACT TRUNCATED AT 250 WORDS)