Ajmalicine Explained

Ajmalicine, also known as δ-yohimbine or raubasine, is an antihypertensive drug used in the treatment of high blood pressure.^[1] It has been marketed under numerous brand names including Card-Lamuran, Circolene, Cristanyl, Duxil, Duxor, Hydroxysarpon, Iskedyl, Isosarpan, Isquebral, Lamuran, Melanex, Raunatin, Saltucin Co, Salvalion, and Sarpan.^[1] It is an alkaloid found naturally in various plants such as Rauvolfia spp., Catharanthus roseus, and Mitragyna speciosa.^{[1] [2] [3]}

Ajmalicine is structurally related to yohimbine, rauwolscine, and other yohimban derivatives.^[4] Like corynanthine, it acts as a α₁-adrenergic receptor antagonist with preferential actions over α₂-adrenergic receptors, underlying its hypotensive rather than hypertensive effects.^{[1] [5]}

Additionally, it is a very strong inhibitor of the CYP2D6 liver enzyme, which is responsible for the breakdown of many drugs. Its binding affinity at this receptor is 3.30 nM.^[6]

Biosynthesis

Two moieties are involved in the biosynthesis of ajmalicine, the terpenoid moiety and the indole moiety.^[7] The terpenoid moiety is synthesized by the MEP pathway. The MEP pathway starts with pyruvate and D-glyceraldehyde-3-phosphate, followed by the involvement of DXS, DXR, MCT, MECS, HDS, and HDR genes. This results in isopentenyl diphosphate and dimethylallyl diphosphate which are then synthesized into secologanin. The indole moiety is brought about by the indole pathway, where tryptophan decarboxylase (TDC) catalyzes the formation of tryptamine from tryptophan. Strictosidine synthase (STR) then catalyzes the formation of strictosidine from the intermediates of the previous pathways. Strictosidine is the common precursor for all terpenoid indole alkaloids. Ajmalicine is finally synthesized under catalysis of strictosidine glucosidase (SGD).

See also

• Corynanthine
• Rauwolscine
• Spegatrine
• Yohimbine

Notes and References

1. Book: Wink M, Roberts MW . Compartmentation of alkaloid synthesis, transport. and storage . Alkaloids: biochemistry, ecology, and medicinal applications . Plenum Press . New York . 1998 . 0-306-45465-3 . https://books.google.com/books?id=bMCzyrAtrvYC&q=ajmalicine&pg=PA451 .
2. Kurz WG, Chatson KB, Constabel F, Kutney JP, Choi LS, Kolodziejczyk P, Sleigh SK, Stuart KL, Worth BR . 6 . Alkaloid Production in Catharanthus roseus cell cultures VIII . Planta Medica . 42 . 1 . 22–31 . May 1981 . 17401876 . 10.1055/s-2007-971541 . 28177495 .
3. León F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ . Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A . Natural Product Communications . 4 . 7 . 907–910 . July 2009 . 19731590 . 9255435 . 10.1177/1934578X0900400705 . 37709142 . free .
4. Book: Roberts MF . Alkaloids: Biochemistry, Ecology, and Medicinal Applications . 1998-06-30 . Springer Science & Business Media . 978-0-306-45465-3 . en.
5. Roquebert J, Demichel P . Inhibition of the alpha 1 and alpha 2-adrenoceptor-mediated pressor response in pithed rats by raubasine, tetrahydroalstonine and akuammigine . European Journal of Pharmacology . 106 . 1 . 203–205 . October 1984 . 6099269 . 10.1016/0014-2999(84)90698-8 .
6. Strobl GR, von Kruedener S, Stöckigt J, Guengerich FP, Wolff T . Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies . Journal of Medicinal Chemistry . 36 . 9 . 1136–1145 . April 1993 . 8487254 . 10.1021/jm00061a004 .
7. Chang K, Chen M, Zeng L, Lan X, Wang Q, Liao Z . Abscisic Acid Enhanced Ajmalicine Biosynthesis in Hairy Roots of Rauvolfia verticillata by Upregulating Expression of the MEP Pathway Genes . Russian Journal of Plant Physiology . 61 . 1 . 136–141 . 2014 . 1021-4437 . 10.1134/S102144371401004X . 255013940 .