Akuammine

Title: Akuammine
CAS Registry Number: 3512-87-6
Additional Names: Vincamajoridine
Molecular Formula: C22H26N2O4
Molecular Weight: 382.45
Percent Composition: C 69.09%, H 6.85%, N 7.32%, O 16.73%
Literature References: From seeds of Picralima nitida (Stapf.) Th. & H. Dur. (P. klaineana Pierre), Apocynaceae: T. A. Henry, T. M. Sharp, J. Chem. Soc. 131, 1950 (1927); T. A. Henry, ibid. 1932, 2759. Identity with vincamajoridine from Vinca major L., Apocynaceae: M. M. Janot et al., Experientia 11, 343 (1955). Structure and chemistry: M. F. Millson et al., ibid. 9, 89 (1953); Saxton, Q. Rev. Chem. Soc. 10, 141 (1956); J. A. Joule, G. F. Smith, J. Chem. Soc. 1962, 312. Revised structure and absolute configuration: L. Olivier et al., Bull. Soc. Chim. Fr. 1965, 868.
Properties: Crystals, decomp 255°. [a]D16 -105.3° (c = 1.31 in pyridine). pKa 7.5. uv max (ethanol): 245, 312 nm (log e 3.96, 3.66). Slightly sol in water, cold alcohol; sol in boiling alcohol, chloroform, acetone.
pKa: pKa 7.5
Optical Rotation: [a]D16 -105.3° (c = 1.31 in pyridine)
Absorption maximum: uv max (ethanol): 245, 312 nm (log e 3.96, 3.66)
Derivative Type: Hydrochloride ethanolate
Molecular Formula: C22H26N2O4.HCl.C2H5OH
Molecular Weight: 464.98
Percent Composition: C 61.99%, H 7.15%, N 6.02%, O 17.20%, Cl 7.62%
Properties: Crystals, mp 232-233°.
Melting point: mp 232-233°
Derivative Type: Methyl ether
Molecular Formula: C23H28N2O4
Molecular Weight: 396.48
Percent Composition: C 69.67%, H 7.12%, N 7.07%, O 16.14%
Properties: Needles from acetone, mp 242-243°. uv max (ethanol): 244, 308 nm (e 11500, 4200).
Melting point: mp 242-243°
Absorption maximum: uv max (ethanol): 244, 308 nm (e 11500, 4200)
Status: This monograph has been retired and is no longer subject to revision or update.
AL 721 Alacepril Alachlor Alafosfalin Alagebrium Chloride

Akuammine
Akuammine.svg
Clinical data
Legal status Legal
Routes Oral, Rectal
Identifiers
CAS number 3512-87-6 N
ATC code None
PubChem CID 6441511
ChemSpider 16735645 YesY
ChEMBL CHEMBL484665 N
Chemical data
Formula C22H26N2O4 
Mol. mass 382.45 g/mol
 N (what is this?)  (verify)

Akuammine, an indole alkaloid also known as vincamajoridine,[1] is the most abundant active alkaloid found in the seeds from the tree Picralima nitida, commonly known as Akuamma.

The dried seeds from this plant are used in traditional medicine throughout West Africa, particularly in Ghana as well as in the Ivory Coast and Nigeria. The seeds are crushed or powdered and taken orally, and are mainly used for the treatment of malaria[2] and diarrhoea, and as a painkiller. An enterprising Ghanaian hospital started manufacturing standardised 250 mg capsules of the powdered P. nitida seed, and sold them around the country where they became widely accepted as a safe and effective pain relief product. This then led researchers to try to discover the active component of the seeds.

P. nitida seeds contain a mixture of alkaloids producing antipyretic and antiinflammatory effects along with analgesia.[3][4] Several of these were shown to bind to opioid receptors in vitro, and two compounds, akuammidine and ψ-akuammigine, were found to be potent μ-opioid agonists, although not particularly selective. Surprisingly the main alkaloid from the seeds, akuammine, was found to be an opioid antagonist when tested in vitro and canceled out the effects of the active agonist components.[5] This finding contradicts the belief by some pharmacological scientists that there are no naturally occurring opioid antagonists.[6]

Given the confirmed activity of the whole seed extract in humans, this makes it likely that akuammine is in fact being metabolised once inside the body to form a metabolite acting as an opioid receptor agonist.

Akuammine is the main alkaloid found in the seeds, comprising 0.56% of the dried powder, indicating that the 250 mg "Picap Capsules" sold commercially should contain approximately 1.4 mg of akuammine, plus 0.085 mg akuammidine and 0.015 mg ψ-akuammigine. Akuammine is structurally related to both yohimbine and mitragynine, both of which are alkaloid plant products with uses in medicine.