Natural compounds boldine and menthol are antagonists of human 5‐HT₃ receptors: implications for treating gastrointestinal disorders

Abstract

The demonstrated 5-HT3 inhibitory effects may be relevant for boldine's and menthol's alleviating properties on FGID and may encourage clinical studies with the compounds or the plant extracts for CINV and IBS treatment. The found receptor-discriminative properties make boldine and (-)-menthol to potentially useful tools for analyzing structural differences between these receptor subtypes.

Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances

“…In recent years, several natural plant ingredients have been identified as 5-HT 3A receptor blockers. These include the two terpenes (-)-menthol and α-thujone [7,23,24], However, effective concentrations of these blockers are typically in the high µM range. The potency of receptor block by ginsenosides from ginseng or gingerols from ginger is higher and lies in the range of 10 to 30 µM [11,25].…”

“…The terpene (-)-menthol which is used against IBS (irritable bowel syndrome) also blocks 5-HT 3A receptors [7,23], but with a lower potency than citronellol. Presently, menthol is the only terpene with a described antiemetic action linked to 5-HT 3A inhibition [7].…”

“…Additionally, receptors are inhibited by many plant derived substances like morphine, cocaine, cannabinoids, terpenes like α-thujone (reviewed by Wallstab 2010) as well as recently shown for (+)-or (-)-nicotine [6] and boldine [7]. A wide range of substances, including divalent cations, alcohols, steroids, anesthetics (propofol), and barbiturates, have been reported to modulate 5-HT 3 receptors [1].…”

Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation

“…Recently, menthol has been hypothesized to exert antiemetic properties by inhibiting the cationic influx through 5-HT 3 receptor (Heimes et al, 2011) and it has been demonstrated to be an allosteric inhibitor of 5-HT 3 receptors using electrophysiological and biochemical methods (Ashoor et al, 2013b;Walstab et al, 2014). 5-HT 3 receptors are expressed by enteric sensory neurons in the mucosal layer and in the nerve cell body of interneurons and motor neurons in the enteric nervous system (Galligan, 2002).…”

Treating Irritable Bowel Syndrome: A Fresh and Minty Approach to an Old Therapy

“…channels [5,6]. Carrying this research one step further, a recent study has also reported the L-menthol can also inhibit 5-HT 3 receptors in vitro, which may explain the decrease in the frequency and amplitude of gut contractions associated with PO [7].…”