{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc}} {{Drugbox | Verifiedfields = changed | verifiedrevid = 477316195 | IUPAC_name = (19α)-16,17-didehydro- 19-methyloxayohimban- 16-carboxylic acid methyl ester | image = Ajmalicine.png | image_class = skin-invert-image | image2 = Ajmalicine-from-xtal-3D-bs-17.png | image_class2 = bg-transparent
<!--Clinical data--> | tradename = | pregnancy_category = | legal_status = Rx-only | routes_of_administration = Oral
<!--Pharmacokinetic data--> | bioavailability = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | CAS_number_Ref = {{cascite|correct|CAS}} | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 4QJL8OX71Z | CAS_number = 483-04-5 | ATC_prefix = none | ATC_suffix = | ChEBI = 2524 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 123325 | PubChem = 251561 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 390541
<!--Chemical data--> | C=21 | H=24 | N=2 | O=3 | smiles = O=C(OC)\C4=C\OC(C5CN3CCc1c([nH]c2ccccc12)C3CC45)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H24N2O3/c1-12-16-10-23-8-7-14-13-5-3-4-6-18(13)22-20(14)19(23)9-15(16)17(11-26-12)21(24)25-2/h3-6,11-12,15-16,19,22H,7-10H2,1-2H3/t12-,15-,16+,19-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = GRTOGORTSDXSFK-XJTZBENFSA-N | melting_point = 262.5 | melting_high = 263 }}
'''Ajmalicine''', also known as '''δ-yohimbine''' or '''raubasine''', is an antihypertensive drug used in the treatment of high blood pressure.<ref name="isbn0-306-45465-3">{{cite book | vauthors = Wink M, Roberts MW | chapter = Compartmentation of alkaloid synthesis, transport. and storage | title = Alkaloids: biochemistry, ecology, and medicinal applications | publisher = Plenum Press | location = New York | year = 1998 | isbn = 0-306-45465-3 | chapter-url = https://books.google.com/books?id=bMCzyrAtrvYC&q=ajmalicine&pg=PA451 }}</ref> 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'''.<ref name="isbn0-306-45465-3"/> It is an alkaloid found naturally in various plants such as ''Rauvolfia'' spp., ''Catharanthus roseus'', and ''Mitragyna speciosa''.<ref name="isbn0-306-45465-3"/><ref name="pmid17401876">{{cite journal | vauthors = Kurz WG, Chatson KB, Constabel F, Kutney JP, Choi LS, Kolodziejczyk P, Sleigh SK, Stuart KL, Worth BR | display-authors = 6 | title = Alkaloid Production in Catharanthus roseus cell cultures VIII | journal = Planta Medica | volume = 42 | issue = 1 | pages = 22–31 | date = May 1981 | pmid = 17401876 | doi = 10.1055/s-2007-971541 | s2cid = 28177495 }}</ref><ref name="pmid19731590">{{cite journal | vauthors = León F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ | title = Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A | journal = Natural Product Communications | volume = 4 | issue = 7 | pages = 907–910 | date = July 2009 | pmid = 19731590 | pmc = 9255435 | doi = 10.1177/1934578X0900400705 | s2cid = 37709142 | doi-access = free }}</ref>
Ajmalicine is structurally related to yohimbine, rauwolscine, and other yohimban derivatives.<ref>{{cite book | vauthors = Roberts MF |title=Alkaloids: Biochemistry, Ecology, and Medicinal Applications |date=1998-06-30 |publisher=Springer Science & Business Media |isbn=978-0-306-45465-3 |language=en}}</ref> Like corynanthine, it acts as a α<sub>1</sub>-adrenergic receptor antagonist with preferential actions over α<sub>2</sub>-adrenergic receptors, underlying its hypotensive rather than hypertensive effects.<ref name="isbn0-306-45465-3"/><ref name="pmid6099269">{{cite journal | vauthors = Roquebert J, Demichel P | title = Inhibition of the alpha 1 and alpha 2-adrenoceptor-mediated pressor response in pithed rats by raubasine, tetrahydroalstonine and akuammigine | journal = European Journal of Pharmacology | volume = 106 | issue = 1 | pages = 203–205 | date = October 1984 | pmid = 6099269 | doi = 10.1016/0014-2999(84)90698-8 }}</ref>
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.<ref name="pmid8487254">{{cite journal | vauthors = Strobl GR, von Kruedener S, Stöckigt J, Guengerich FP, Wolff T | title = Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies | journal = Journal of Medicinal Chemistry | volume = 36 | issue = 9 | pages = 1136–1145 | date = April 1993 | pmid = 8487254 | pmc = | doi = 10.1021/jm00061a004 }} </ref>
== Biosynthesis == Two moieties are involved in the biosynthesis of ajmalicine, the terpenoid moiety and the indole moiety.<ref name="issn10214437">{{cite journal | vauthors = Chang K, Chen M, Zeng L, Lan X, Wang Q, Liao Z | title = Abscisic Acid Enhanced Ajmalicine Biosynthesis in Hairy Roots of Rauvolfia verticillata by Upregulating Expression of the MEP Pathway Genes | journal = Russian Journal of Plant Physiology | volume = 61 | issue = 1 | pages = 136–141 | year = 2014 | issn = 1021-4437 | doi = 10.1134/S102144371401004X | s2cid = 255013940 }}</ref> 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).
thumb|center|class=skin-invert-image|Biosynthetic pathway of ajmalicine. Reconstruction of figure 1 in Chang, K. (2014).<ref name="issn10214437">{{cite journal | vauthors = Chang K, Chen M, Zeng L, Lan X, Wang Q, Liao Z | title = Abscisic Acid Enhanced Ajmalicine Biosynthesis in Hairy Roots of Rauvolfia verticillata by Upregulating Expression of the MEP Pathway Genes | journal = Russian Journal of Plant Physiology | volume = 61 | issue = 1 | pages = 136–141 | year = 2014 | issn = 1021-4437 | doi = 10.1134/S102144371401004X | s2cid = 255013940 }}</ref>
== See also == * Corynanthine * Rauwolscine * Spegatrine * Yohimbine
== References == {{Reflist}}
{{Antihypertensives}} {{Adrenergic receptor modulators}} {{Tryptamines}}
Category:Alkaloids found in Rauvolfia Category:Alpha-1 blockers Category:Antihypertensive agents Category:Quinolizidine alkaloids Category:Mitragyna alkaloids Category:Tryptamine alkaloids Category:Indoloquinolizines Category:Vinca alkaloids Category:Methyl esters Category:Heterocyclic compounds with 5 rings