Kavain
| |
| |
| Names | |
|---|---|
| Preferred IUPAC name
4-Methoxy-6-[(E)-2-phenylethenyl]-5,6-dihydro-2H-pyran-2-one | |
| Other names
(E)-4-Methoxy-6-styryl-5,6-dihydro-2H-pyran-2-one
Kawain | |
| Identifiers | |
3D model (JSmol)
|
|
| ChemSpider | |
| ECHA InfoCard | 100.007.189 |
| KEGG | |
PubChemCID
|
|
| UNII | |
CompTox Dashboard(EPA)
|
|
| |
| |
| Properties | |
| C14H14O3 | |
| Molar mass | 230.263g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
| |
Kavainis the mainkavalactonefound mostly in therootsof thekavaplant.
Pharmacology
[edit]Kavain hasanticonvulsiveproperties, attenuatingvascularsmooth musclecontraction through interactions with voltage-dependentNa+andCa2+channels.[1]How this effect is mediated, and to what extent this mechanism is involved in theanxiolyticandanalgesiceffects of kavalactones on thecentral nervous system,is unknown. The recent finding that kavain canreversibly inhibitbothmonoamine oxidase Aandmonoamine oxidase Bsuggests that kavain may exert some of its effects by modulatingserotonin,norepinephrine,anddopaminesignaling.[2]
However, the precise mechanisms underlying thepsychotropic,sedative,andanxiolyticactions of kavain and related kavalactones are still debated. Direct binding to thebenzodiazepine/flumazenilbinding siteof theGABA-A receptordoes not occur with kavainenantiomers.[3]Many studies involved kava extracts from different plant parts and are, therefore, not applicable to kavain itself. In 2016, kavain was shown to bind at the extrasynaptic α4β2δ GABAA receptor andpotentiateGABAefficacy, similarly tobarbiturates.[4]
A comparative review ofin-vivostudies with kavain (and related kavapyrones) to commonly usedantiepilepticdrugs andmood stabilizersaffecting ion fluxes indicates that the kavapyrones are weakly Na+ antagonistic and therefore antiepileptic. They also have pronouncedL- typeCa2+channelantagonistic properties and act as a positive modulator of the early K+ outward current, which contribute to mood stabilizing properties similar tolamotrigine.[5]
Kavain and analogs remain interesting fordrug discoveryagainst a variety of cellular targets, includingP-glycoprotein(Pgp),cytochrome P450,andcyclo-oxygenase(COX) enzymes among others.[6]
See also
[edit]References
[edit]- ^Bradić, I; Pasini, M (1975). "Hirschsprung's disease - therapy and results".Acta Chirurgica Iugoslavica.22(2): 183–95.PMID1235738.
- ^Prinsloo, Denise; van Dyk, Sandra; Petzer, Anél; Petzer, Jacobus P. (2019-09-20)."Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum)".Planta Medica.85(14/15): 1136–1142.doi:10.1055/a-1008-9491.ISSN0032-0943.PMID31539917.
- ^Boonen, Georg; Häberlein, Hans (2007). "Influence of Genuine Kavapyrone Enantiomers on the GABAABinding Site".Planta Medica.64(6): 504–6.doi:10.1055/s-2006-957502.PMID9776662.S2CID45511040.
- ^Chua HC, Christensen ET, Hoestgaard-Jensen K, Hartiadi LY, Ramzan I, Jensen AA, Absalom NL, Chebib M (2016)."Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism".PLOS ONE.11(6): e0157700.Bibcode:2016PLoSO..1157700C.doi:10.1371/journal.pone.0157700.PMC4917254.PMID27332705.
- ^Grunze, Heinz; Langosch, Jens; Schirrmacher, Karin; Bingmann, Dieter; Von Wegerer, Jörg; Walden, Jörg (2001). "Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers - a review".Progress in Neuro-Psychopharmacology and Biological Psychiatry.25(8): 1555–70.doi:10.1016/S0278-5846(01)00208-1.PMID11642654.S2CID41325450.
- ^Rowe, A.; Narlawar, R.; w. Groundwater, P.; Ramzan, I. (2011). "Kavalactone Pharmacophores for Major Cellular Drug Targets".Mini Reviews in Medicinal Chemistry.11(1): 79–83.doi:10.2174/138955711793564088.PMID21034404.