Alstonine

{{Short description|Chemical compound}}

{{Drugbox

| drug_name =

| IUPAC_name = (19α,20α)-16-(Methoxycarbonyl)-19-methyl-3,4,5,6,16,17-hexadehydro-18-oxayohimban-4-ium

| image = File:Alstonine2DACS3.svg

| width = 200

| image2 = File:Alstonine.png

| width2 = 200

| CAS_number = 642-18-2

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = SB0M27Q90X

| ATCvet =

| ATC_prefix = none

| ATC_suffix =

| PubChem = 441979

| ChEBI = 2612

| ChemSpiderID = 149308

| chemical_formula =

| C=21 | H=21 | N=2 | O=3

| smiles = O=C(OC)\C1=C\O[C@H]([C@H]5[C@@H]1Cc3[n+](ccc4c2ccccc2[nH]c34)C5)C

| StdInChIKey = WYTGDNHDOZPMIW-RCBQFDQVSA-O

| StdInChI = InChI=1S/C21H20N2O3/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/h3-8,11-12,15-16H,9-10H2,1-2H3/p+1/t12-,15-,16-/m0/s1

}}

Alstonine is a pentacyclic alkaloid and putative antipsychotic constituent of various plant species including Alstonia boonei, Catharanthus roseus, Picralima nitida, Rauvolfia afra and Rauvolfia vomitoria.{{cite journal | vauthors = Elisabetsky E, Costa-Campos L | title = The alkaloid alstonine: a review of its pharmacological properties | journal = Evidence-Based Complementary and Alternative Medicine | volume = 3 | issue = 1 | pages = 39–48 | date = March 2006 | pmid = 16550222 | pmc = 1375234 | doi = 10.1093/ecam/nek011 }} In preclinical studies alstonine attenuates MK-801-induced hyperlocomotion, working memory deficit and social withdrawal.{{cite journal | vauthors = Linck VM, Bessa MM, Herrmann AP, Iwu MM, Okunji CO, Elisabetsky E | title = 5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 36 | issue = 1 | pages = 29–33 | date = January 2012 | pmid = 21925231 | doi = 10.1016/j.pnpbp.2011.08.022 | s2cid = 3236174 | doi-access = free }} It also possesses anxiolytic-like effects in preclinical studies, attenuates amphetamine-induced lethality and stereotypy as well as apomorphine-induced stereotypy, and attenuates haloperidol-induced catalepsy.{{cite journal | vauthors = Linck VM, Herrmann AP, Piato AL, Detanico BC, Figueiró M, Flório J, Iwu MM, Okunji CO, Leal MB, Elisabetsky E | display-authors = 6 | title = Alstonine as an antipsychotic: effects on brain amines and metabolic changes | journal = Evidence-Based Complementary and Alternative Medicine | volume = 2011 | issue = 418597 | pages = 418597 | date = July 2011 | pmid = 19189988 | pmc = 3140158 | doi = 10.1093/ecam/nep002 }} These effects appear to be mediated by stimulation of the 5-HT_2C receptor.{{cite book | vauthors = Meltzer HY | title = Current Antipsychotics | chapter = Serotonergic Mechanisms as Targets for Existing and Novel Antipsychotics | series = Handbook of Experimental Pharmacology | volume = 212 | issue = 212 | pages = 87–124 | year = 2012 | pmid = 23129329 | doi = 10.1007/978-3-642-25761-2_4 | publisher = Springer | location = Berlin Heidelberg | isbn = 978-3-642-25761-2 | veditors = Gross G, Geyer MA }} In addition, alstonine, similarly to clozapine, indirectly inhibits the reuptake of glutamate in hippocampal slices.{{cite journal | vauthors = Herrmann AP, Lunardi P, Pilz LK, Tramontina AC, Linck VM, Okunji CO, Gonçalves CA, Elisabetsky E | display-authors = 6 | title = Effects of the putative antipsychotic alstonine on glutamate uptake in acute hippocampal slices | journal = Neurochemistry International | volume = 61 | issue = 7 | pages = 1144–1150 | date = December 2012 | pmid = 22940693 | doi = 10.1016/j.neuint.2012.08.006 | s2cid = 14234269 | doi-access = free }} Unlike clozapine however, the effect of which is abolished by the D₂ receptor agonist apomorphine, alstonine requires 5-HT_2A and 5-HT_2C receptors to produce this effect, as it is abolished by antagonists of these receptors. Also unlike clozapine, alstonine lacks pro-convulsant activity in mice.{{cite journal | vauthors = Costa-Campos L, Iwu M, Elisabetsky E | title = Lack of pro-convulsant activity of the antipsychotic alkaloid alstonine | journal = Journal of Ethnopharmacology | volume = 93 | issue = 2–3 | pages = 307–310 | date = August 2004 | pmid = 15234769 | doi = 10.1016/j.jep.2004.03.056 }}