Corynantheidine (Synonyms: (-)-Corynantheidine, 9-demethoxy Mitragynine)

Corynantheidine is an alkaloid that has been found in M. speciosa (Kratom in Thai) and has antinociceptive activity.^1,2 It is a partial agonist of the μ-opioid receptor that lacks β-arrestin recruitment activity.¹ Corynantheidine selectively binds to μ-opioid receptors over κ- and δ-opioid receptors (K_is = 57.1, 385.4, and 172 nM, respectively, for the mouse receptors) and is selective for the μ-opioid receptor (EC₅₀ = 104.24 nM) over the κ- and δ-opioid receptors, for which it has no activity, in [³⁵S]GTPγS assays. It also binds to α_1D- and α_2A-adrenergic receptors and NMDA receptors (K_is = 41, 74, and 83 nM, respectively, for the human receptors), among others.^1,2 Corynantheidine (10-100 nmol, i.c.v.) increases the latency to tail withdrawal in the tail-flick test in mice.¹

1.Chakraborty, S., Uprety, R., Daibani, A.E., et al.Kratom alkaloids as probes for opioid receptor function: Pharmacological characterization of minor indole and oxindole alkaloids from kratomACS Chem. Neurosci.12(14)2661-2678(2021) 2.Obeng, S., Kamble, S.H., Reeves, M.E., et al.Investigation of the adrenergic and opioid binding affinities, metabolic stability, plasma protein binding properties, and functional effects of selected indole-based kratom alkaloidsJ. Med. Chem.63(1)433-439(2020)