1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

Naunyn-Schmiedeberg's archives of pharmacology

PubMedID: 6255348

Rommelspacher H, Nanz C, Borbe HO, Fehske KJ, Müller WE, Wollert U. 1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding. Naunyn Schmiedebergs Arch Pharmacol. 1980;314(1):97-100.
The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.