indeloxazine

{{short description|Antidepressant and cerebral activator}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 444576847

| IUPAC_name = 2-(3H-Inden-4-yloxymethyl)morpholine

| image = Indeloxazine.svg

| width = 200

| tradename =

| pregnancy_category =

| legal_status = Discontinued

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 60929-23-9

| ATC_prefix = None

| ATC_suffix =

| PubChem = 3704

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3576

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

| UNII = 834M09R1KM

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08077

| C=14 | H=17 | N=1 | O=2

| smiles = O(c1cccc2\C=C/Cc12)CC3OCCNC3

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C14H17NO2/c1-3-11-4-2-6-14(13(11)5-1)17-10-12-9-15-7-8-16-12/h1-4,6,12,15H,5,7-10H2

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = MADRVGBADLFHMO-UHFFFAOYSA-N

| synonyms = CI-874, YM-08054

}}

Indeloxazine (INN; trade names Elen and Noin) is an antidepressant and cerebral activator{{cite journal | vauthors = Kojima T, Niigata K, Fujikura T, Tachikawa S, Nozaki Y, Kagami S, Takahashi K | title = Syntheses of (+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride (YM-08054, indeloxazine hydrochloride) and its derivatives with potential cerebral-activating and antidepressive properties | journal = Chemical & Pharmaceutical Bulletin | volume = 33 | issue = 9 | pages = 3766–3774 | date = September 1985 | pmid = 4092278 | doi = 10.1248/cpb.33.3766 | doi-access = free }}{{cite journal | vauthors = Hayes AG, Chang T | title = Determination of indeloxazine, a new antidepressant agent, in human plasma by gas-liquid chromatography with electron-capture detection | journal = Journal of Chromatography | volume = 272 | issue = 1 | pages = 176–180 | date = January 1983 | pmid = 6841538 | doi = 10.1016/s0378-4347(00)86115-0 }} that was marketed in Japan and South Korea by Yamanouchi Pharmaceutical Co., Ltd for the treatment of psychiatric symptoms associated with cerebrovascular diseases, namely depression resulting from stroke, emotional disturbance, and avolition.{{cite book | url = https://books.google.com/books?id=5GpcTQD_L2oC&q=indeloxazine&pg=PA548 | title = Index nominum, international drug ... - Google Books | isbn = 978-3-88763-075-1 | year = 2000 | publisher = Taylor & Francis }}{{cite book | url = https://books.google.com/books?id=A0THacd46ZsC&q=Indeloxazine | title = Dictionary of pharmacological agents - Google Books | isbn = 978-0-412-46630-4 | vauthors = Ganellin CR, Triggle JD, MacDonald F | year = 1997 | publisher = CRC Press }} It was marketed from 1988 to 1998, when it was removed from the market reportedly for lack of effectiveness.{{cite journal | vauthors = Hayashi K, Hashimoto K, Yanagi M, Umeda T, Hama R | title = Drug approval in Japan questioned | journal = Lancet | volume = 352 | issue = 9126 | pages = 491 | date = August 1998 | pmid = 9708787 | doi = 10.1016/s0140-6736(05)79232-1 | s2cid = 43687432 | doi-access = free }}

Indeloxazine acts as a serotonin releasing agent, norepinephrine reuptake inhibitor, and NMDA receptor antagonist.{{cite journal | vauthors = Yamaguchi T, Ohyama M, Suzuki M, Ozawa Y, Hatanaka K, Hidaka K, Yamamoto M | title = Neurochemical and behavioral characterization of potential antidepressant properties of indeloxazine hydrochloride | journal = Neuropharmacology | volume = 37 | issue = 9 | pages = 1169–1176 | date = September 1998 | pmid = 9833647 | doi = 10.1016/s0028-3908(98)00009-4 | s2cid = 12707551 }}{{cite journal | vauthors = Kaneko S, Sugimura M, Inoue T, Satoh M | title = Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding | journal = European Journal of Pharmacology | volume = 207 | issue = 2 | pages = 119–128 | date = June 1991 | pmid = 1652446 | doi = 10.1016/0922-4106(91)90086-w }} It has been found to enhance acetylcholine release in the rat forebrain through activation of the 5-HT₄ receptor via its action as a serotonin releasing agent.{{cite journal | vauthors = Peñas-Cazorla R, Vilaró MT | title = Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations | journal = Brain Structure & Function | volume = 220 | issue = 6 | pages = 3413–3434 | date = November 2015 | pmid = 25183542 | doi = 10.1007/s00429-014-0864-z | hdl-access = free | s2cid = 14116338 | hdl = 10261/124736 }}{{cite journal | vauthors = Yamaguchi T, Suzuki M, Yamamoto M | title = Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 356 | issue = 6 | pages = 712–720 | date = December 1997 | pmid = 9453456 | doi = 10.1007/pl00005110 | url = http://link.springer.de/link/service/journals/00210/bibs/7356006/73560712.htm | access-date = 2010-01-11 | url-status = dead | s2cid = 7800009 | archive-url = https://web.archive.org/web/19991008020023/http://link.springer.de/link/service/journals/00210/bibs/7356006/73560712.htm | archive-date = 1999-10-08 }}{{cite journal | vauthors = Yamamoto M, Takahashi K, Ohyama M, Sasamata M, Yatsugi S, Okada M, Endoh H | title = Possible involvement of central cholinergic system in ameliorating effects of indeloxazine, a cerebral activator, on disturbance of learning behavior in rats | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 18 | issue = 3 | pages = 603–613 | date = May 1994 | pmid = 8078992 | doi = 10.1016/0278-5846(94)90016-7 | s2cid = 11703415 }} The drug has been found to possess nootropic,{{cite journal | vauthors = Ogawa N, Haba K, Sora YH, Higashida A, Sato H, Ogawa S | title = Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance | journal = Clinical Therapeutics | volume = 10 | issue = 6 | pages = 704–711 | date = 1988 | pmid = 3219685 }}{{cite journal | vauthors = Yamamoto M, Shimizu M | title = Cerebral activating properties of indeloxazine hydrochloride | journal = Neuropharmacology | volume = 26 | issue = 7A | pages = 761–770 | date = July 1987 | pmid = 3627384 | doi = 10.1016/0028-3908(87)90239-5 | s2cid = 46153252 }} neuroprotective,{{cite journal | vauthors = Ogawa N, Haba K, Yoshikawa H, Ono T, Mizukawa K | title = Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced depletion of brain acetylcholine levels in gerbils | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 61 | issue = 2 | pages = 285–288 | date = August 1988 | pmid = 3187197 }}{{cite journal | vauthors = Yamamoto M, Shimizu M, Sakamoto N, Ohtomo H, Kogure K | title = Protective effects of indeloxazine hydrochloride on cerebral ischemia in animals | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 290 | issue = 1 | pages = 16–24 | date = November 1987 | pmid = 3446040 }}{{cite journal | vauthors = Shimizu-Sasamata M, Terai M, Harada M, Yamamoto M | title = Anti-hypoxic and anti-ischemic actions of indeloxazine hydrochloride and its optical isomers: possible involvement of cerebral energy metabolism | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 324 | pages = 33–46 | date = 1993 | pmid = 8297184 }}{{cite journal | vauthors = Yamamoto M, Shimizu M | title = Effects of indeloxazine hydrochloride (YM-08054) on anoxia | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 286 | issue = 2 | pages = 272–281 | date = April 1987 | pmid = 3592867 }} anticonvulsant,{{cite journal | vauthors = Nakamura J, Anraku T, Shirouzu M, Iwashita Y, Nakazawa Y | title = Effects of indeloxazine HCl on kindled amygdaloid seizures in rats: comparison with the effects of phenytoin, diazepam, ethanol, and imipramine | journal = Pharmacology, Biochemistry, and Behavior | volume = 45 | issue = 2 | pages = 445–450 | date = June 1993 | pmid = 8327550 | doi = 10.1016/0091-3057(93)90263-s | s2cid = 26761718 }} and antidepressant-like effects in animal models.