Indeloxazine

Indeloxazine (INN) (Elen, Noin) is an antidepressant and cerebral activator^[1][2] 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.^[3][4] It was marketed from 1988^[4] to 1998, when it was removed from the market reportedly for lack of effectiveness.^[5]

Indeloxazine

Clinical data
Other names	CI-874, YM-08054
ATC code	None
Legal status
Legal status	Discontinued
Identifiers
IUPAC name 2-(3H-Inden-4-yloxymethyl)morpholine
CAS Number	60929-23-9 Y
PubChem CID	3704
ChemSpider	3576 Y
UNII	834M09R1KM
KEGG	D08077 Y
CompTox Dashboard (EPA)	DTXSID30866833
Chemical and physical data
Formula	C14H17NO2
Molar mass	231.295 g·mol−1
3D model (JSmol)	Interactive image
SMILES O(c1cccc2\C=C/Cc12)CC3OCCNC3
InChI InChI=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 Y Key:MADRVGBADLFHMO-UHFFFAOYSA-N Y
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Indeloxazine acts as a serotonin releasing agent, norepinephrine reuptake inhibitor, and NMDA receptor antagonist.^[6][7] 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.^[8][9][10] The drug has been found to possess nootropic,^[11][12] neuroprotective,^{[13][14][15][16]} anticonvulsant,^[17] and antidepressant-like effects in animal models.^[1][6]

References

1. Kojima T, Niigata K, Fujikura T, Tachikawa S, Nozaki Y, Kagami S, Takahashi K (September 1985). "Syntheses of (+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride (YM-08054, indeloxazine hydrochloride) and its derivatives with potential cerebral-activating and antidepressive properties". Chemical & Pharmaceutical Bulletin. 33 (9): 3766–3774. doi:10.1248/cpb.33.3766. PMID 4092278.
2. Hayes AG, Chang T (January 1983). "Determination of indeloxazine, a new antidepressant agent, in human plasma by gas-liquid chromatography with electron-capture detection". Journal of Chromatography. 272 (1): 176–180. doi:10.1016/s0378-4347(00)86115-0. PMID 6841538.
3. Index nominum, international drug ... - Google Books. Taylor & Francis. 2000. ISBN 978-3-88763-075-1.
4. Ganellin CR, Triggle JD, MacDonald F (1997). Dictionary of pharmacological agents - Google Books. CRC Press. ISBN 978-0-412-46630-4.
5. Hayashi K, Hashimoto K, Yanagi M, Umeda T, Hama R (August 1998). "Drug approval in Japan questioned". Lancet. 352 (9126): 491. doi:10.1016/s0140-6736(05)79232-1. PMID 9708787. S2CID 43687432.
6. Yamaguchi T, Ohyama M, Suzuki M, Ozawa Y, Hatanaka K, Hidaka K, Yamamoto M (September 1998). "Neurochemical and behavioral characterization of potential antidepressant properties of indeloxazine hydrochloride". Neuropharmacology. 37 (9): 1169–1176. doi:10.1016/s0028-3908(98)00009-4. PMID 9833647. S2CID 12707551.
7. Kaneko S, Sugimura M, Inoue T, Satoh M (June 1991). "Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding". European Journal of Pharmacology. 207 (2): 119–128. doi:10.1016/0922-4106(91)90086-w. PMID 1652446.
8. Peñas-Cazorla R, Vilaró MT (November 2015). "Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations". Brain Structure & Function. 220 (6): 3413–3434. doi:10.1007/s00429-014-0864-z. hdl:10261/124736. PMID 25183542. S2CID 14116338.
9. Yamaguchi T, Suzuki M, Yamamoto M (December 1997). "Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors". Naunyn-Schmiedeberg's Archives of Pharmacology. 356 (6): 712–720. doi:10.1007/pl00005110. PMID 9453456. S2CID 7800009. Archived from the original on 1999-10-08. Retrieved 2010-01-11.
10. Yamamoto M, Takahashi K, Ohyama M, Sasamata M, Yatsugi S, Okada M, Endoh H (May 1994). "Possible involvement of central cholinergic system in ameliorating effects of indeloxazine, a cerebral activator, on disturbance of learning behavior in rats". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 18 (3): 603–613. doi:10.1016/0278-5846(94)90016-7. PMID 8078992. S2CID 11703415.
11. Ogawa N, Haba K, Sora YH, Higashida A, Sato H, Ogawa S (1988). "Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance". Clinical Therapeutics. 10 (6): 704–711. PMID 3219685.
12. Yamamoto M, Shimizu M (July 1987). "Cerebral activating properties of indeloxazine hydrochloride". Neuropharmacology. 26 (7A): 761–770. doi:10.1016/0028-3908(87)90239-5. PMID 3627384. S2CID 46153252.
13. Ogawa N, Haba K, Yoshikawa H, Ono T, Mizukawa K (August 1988). "Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced depletion of brain acetylcholine levels in gerbils". Research Communications in Chemical Pathology and Pharmacology. 61 (2): 285–288. PMID 3187197.
14. Yamamoto M, Shimizu M, Sakamoto N, Ohtomo H, Kogure K (November 1987). "Protective effects of indeloxazine hydrochloride on cerebral ischemia in animals". Archives Internationales de Pharmacodynamie et de Therapie. 290 (1): 16–24. PMID 3446040.
15. Shimizu-Sasamata M, Terai M, Harada M, Yamamoto M (1993). "Anti-hypoxic and anti-ischemic actions of indeloxazine hydrochloride and its optical isomers: possible involvement of cerebral energy metabolism". Archives Internationales de Pharmacodynamie et de Therapie. 324: 33–46. PMID 8297184.
16. Yamamoto M, Shimizu M (April 1987). "Effects of indeloxazine hydrochloride (YM-08054) on anoxia". Archives Internationales de Pharmacodynamie et de Therapie. 286 (2): 272–281. PMID 3592867.
17. Nakamura J, Anraku T, Shirouzu M, Iwashita Y, Nakazawa Y (June 1993). "Effects of indeloxazine HCl on kindled amygdaloid seizures in rats: comparison with the effects of phenytoin, diazepam, ethanol, and imipramine". Pharmacology, Biochemistry, and Behavior. 45 (2): 445–450. doi:10.1016/0091-3057(93)90263-s. PMID 8327550. S2CID 26761718.