title: Orally active opioid compounds from a non-poppy source.
abstract: The basic science and clinical use of morphine and other "opioid" drugs are based almost exclusively on the extracts or analogues of compounds isolated from a single source, the opium poppy (Papaver somniferum). However, it now appears that biological diversity has evolved an alternative source. Specifically, at least two alkaloids isolated from the plant Mitragyna speciosa, mitragynine ((E)-2-[(2S,3S)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[3,2-h]quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester; 9-methoxy coryantheidine; MG) and 7-hydroxymitragynine (7-OH-MG), and several synthetic analogues of these natural products display centrally mediated (supraspinal and spinal) antinociceptive (analgesic) activity in various pain models. Several characteristics of these compounds suggest a classic "opioid" mechanism of action: nanomolar affinity for opioid receptors, competitive interaction with the opioid receptor antagonist naloxone, and two-way analgesic cross-tolerance with morphine. However, other characteristics of the compounds suggest novelty, particularly chemical structure and possible greater separation from side effects. We review the chemical and pharmacological properties of these compounds.
authors.affiliation: Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, Pennsylvania 19140, USA. robert.raffa@temple.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Raffa
authors.forename: Jaclyn R
authors.initials: JR
authors.lastname: Beckett
authors.forename: Vivek N
authors.initials: VN
authors.lastname: Brahmbhatt
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Ebinger
authors.forename: Chrisjon A
authors.initials: CA
authors.lastname: Fabian
authors.forename: Justin R
authors.initials: JR
authors.lastname: Nixon
authors.forename: Steven T
authors.initials: ST
authors.lastname: Orlando
authors.forename: Chintan A
authors.initials: CA
authors.lastname: Rana
authors.forename: Ali H
authors.initials: AH
authors.lastname: Tejani
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tomazic
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D046948:Secologanin Tryptamine Alkaloids / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D019966:Substance-Related Disorders
chemical_list: D000701:Analgesics, Opioid; D046948:Secologanin Tryptamine Alkaloids; C482678:7-hydroxymitragynine; C001801:mitragynine