Exploration of the potential neurotransmitter or neuromodulator-like properties of harmine: evidence from synthesis to synaptic modulation
Frontiers in Pharmacology July 7, 2025 Zhejun Xie, Ning Cao, Manlin Li et al. 2 citations
Harmine, an endogenous compound whose levels vary with physiological and disease states, may act as a neurotransmitter or neuromodulator. The protein APMAP-X1 catalyzes the formation of tetrahydroharmine, which is then oxidized by MPO to produce harmine. Harmine is metabolized, taken up, and released within the synaptic cleft, and it regulates neurotransmitter transporter expression. It binds to GPR85 and CLIC2 receptors in the central nervous system, inhibiting GPR85 and inducing cellular depolarization. These findings suggest harmine has neurotransmitter-like properties and may function as an endogenous neuromodulator, though direct evidence as a neurotransmitter remains limited.