関: tropisetron hydrochloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/22 17:27:52」(JST)

wiki en

Tropisetron (INN) is a serotonin 5-HT₃ receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy, although it has been used experimentally as an analgesic in cases of fibromyalgia.^[1] The drug is available in a 5 mg oral preparation or in 2 mg intravenous form. It is marketed by Novartis in Europe, Australia, New Zealand, Japan, South Korea and the Philippines as Navoban, but is not available in the U.S. It is also available from Novell Pharmaceutical Laboratories and marketed in several Asian countries as Setrovel

Pharmacology[edit]

Tropisetron acts as both a selective 5-HT₃ receptor antagonist and α₇-nicotinic receptor agonist.^[2]^[3]

Adverse effects[edit]

Tropisetron is a well-tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. Hypotension, transient liver enzyme elevation, immune hypersensitivity syndromes and extrapyramidal side effects have also been associated with its use on at least one occasion.There have been no significant drug interactions reported with this drug's use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.

Other uses[edit]

As a biological stain and as trypanocide.

References[edit]

^ Muller, W.; T. Stratz (2004). "Local treatment of tendinopathies and myofascial pain syndromes with the 5-HT3 receptor antagonist tropisetron". Scand J Rheumatic Suppl. 119 (119): 44–48. PMID 15515413. Retrieved 2007-05-17. Cite uses deprecated parameters (help)
^ Macor JE, Gurley D, Lanthorn T, Loch J, Mack RA, Mullen G, Tran O, Wright N, Gordon JC (February 2001). "The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist". Bioorganic & Medicinal Chemistry Letters 11 (3): 319–21. doi:10.1016/S0960-894X(00)00670-3. PMID 11212100. Cite uses deprecated parameters (help)
^ Cui R, Suemaru K, Li B, Kohnomi S, Araki H (May 2009). "Tropisetron attenuates naloxone-induced place aversion in single-dose morphine-treated rats: role of alpha7 nicotinic receptors". European Journal of Pharmacology 609 (1–3): 74–7. doi:10.1016/j.ejphar.2008.12.051. PMID 19374878. Cite uses deprecated parameters (help)

External links[edit]

Official site
Navoban data sheet

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 麻酔後ケア病棟における合併症発生の概要 overview of complications occurring in the post anesthesia care unit
2. 化学療法誘発性悪心および嘔吐の予防および治療 prevention and treatment of chemotherapy induced nausea and vomiting
3. 放射線療法による悪心および嘔吐：予防と治療 radiotherapy induced nausea and vomiting prophylaxis and treatment
4. 悪性腫瘍関連胃不全麻痺：病態生理およびマネージメント malignancy associated gastroparesis pathophysiology and management
5. 小児における扁桃摘出、アデノイド切除：術前および術中のケア tonsillectomy and or adenoidectomy in children preoperative and intraoperative care

English Journal

The Neuroprotective Effect of Tropisetron on Vincristine-Induced Neurotoxicity.

Barzegar-Fallah A1, Alimoradi H2, Mehrzadi S3, Barzegar-Fallah N4, Zendedel A5, Abbasi A6, Dehpour AR7.Author information 1Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.2Department of Pharmacology and Toxicology, University of Otago, P.O. Box 913, Dunedin, New Zealand.3Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.4Department of Pharmacology, Islamic Azad University of Pharmaceutical Sciences, Tehran, Iran.5Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Germany.6Department of Pathology, Tehran University of Medical Science, Tehran, Iran.7Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com.AbstractVincristine (VCR) peripheral neuropathy is a dose-limiting side effect. Several studies have shown that tropisetron, a 5-HT3 receptor antagonist, exerts anti-inflammatory and immunomodulatory properties. Current study was designed to investigate a suppressive effect of tropisetron on VCR-induced neuropathy and whether this effect exerts through the 5-HT3 receptor or not. Neuropathy was induced in rats by administration of vincristine (0.5 mg/kg, 3 intraperitoneal injections on alternate days) and in treatment group, tropisetron (3mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT3 receptor agonist (15mg/kg); tropisetron (3mg/kg) plus mCPBG (15mg/kg); granisetron, another selective 5-HT3 receptor antagonist (3mg/kg) were administered intraperitoneally 1h prior to vincristine injection. Hot plate, open field tests (total distance moved, mean velocity and percentage of total duration of the movement) and Motor Nerve Conduction Velocity (MNCV) were performed to evaluate the sensory and motor neuropathy. Further, plasma levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) and the level of TNF-α in sciatic nerve were assessed as well as histological examination. In only VCR-treated rats hot plate latencies were significantly increased, total distance moved, mean velocity, total duration of the movement and sciatic MNCV significantly decreased compared with control. In tropisetron and tropisetron plus mCPBG groups, one injection of tropisetron prior to each VCR injection robustly diminished TNF-α and IL-2 levels, and also prevented mixed sensory-motor neuropathy, as indicated by less mortality rate, better general conditions, behavioral and electrophysiological studies. Moreover, pathological evidence confirmed the results obtained from other findings. But granisetron and mCPBG had no significant effect on the mentioned parameters. In conclusion, these studies demonstrate that tropisetron significantly suppressed VCR-induced neuropathy and could be a neuroprotective agent for prevention of VCR-induced neuropathy via a receptor-independent pathway.
Neurotoxicology.Neurotoxicology.2013 Dec 26. pii: S0161-813X(13)00183-6. doi: 10.1016/j.neuro.2013.12.002. [Epub ahead of print]
Vincristine (VCR) peripheral neuropathy is a dose-limiting side effect. Several studies have shown that tropisetron, a 5-HT3 receptor antagonist, exerts anti-inflammatory and immunomodulatory properties. Current study was designed to investigate a suppressive effect of tropisetron on VCR-induced neu
PMID 24374478

Prophylaxis of intra- and postoperative nausea and vomiting in patients during cesarean section in spinal anesthesia.

Voigt M, Fröhlich CW, Hüttel C, Kranke P, Mennen J, Boessneck O, Lenz C, Erbes T, Ernst J, Kerger H.Author information Evangelian Deaconry Hospital, Freiburg, Germany.AbstractBACKGROUND: This paper describes a randomized prospective study conducted in 308 patients undergoing caesarean section in spinal anaesthesia at a single hospital between 2010 and 2012 to find a suitable anti-emetic strategy for these patients.
Medical science monitor : international medical journal of experimental and clinical research.Med Sci Monit.2013 Nov 14;19:993-1000. doi: 10.12659/MSM.889597.
BACKGROUND: This paper describes a randomized prospective study conducted in 308 patients undergoing caesarean section in spinal anaesthesia at a single hospital between 2010 and 2012 to find a suitable anti-emetic strategy for these patients.MATERIAL AND METHODS: Spinal anesthesia was performed in
PMID 24226381

P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors.

Krimon S, Araldi D, do Prado FC, Tambeli CH, Oliveira-Fusaro MC, Parada CA.Author information Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Brazil.AbstractIt has been described that endogenous ATP via activation of P2X3 and P2X2/3 receptors contributes to inflammatory nociception in different models, including the formalin injected in subcutaneous tissue of the rat's hind paw. In this study, we have evaluated whether TRPA1, 5-HT3 and 5-HT1A receptors, whose activation is essential to formalin-induced inflammatory nociception, are involved in the nociception induced by activation of P2X3 receptors on subcutaneous tissue of the rat's hind paw. We have also evaluated whether the activation of P2X3 receptors increases the susceptibility of primary afferent neurons to formalin action modulated by activation of TRPA1, 5-HT3 or 5-HT1A receptors. Nociceptive response intensity was measured by observing the rat's behavior and considering the number of times the animal reflexively raised its hind paw (flinches) in 60min. Local subcutaneous administration of the selective TRPA1, 5-HT3 or 5-HT1A receptor antagonists HC 030031, tropisetron and WAY 100,135, respectively, prevented the nociceptive responses induced by the administration in the same site of the non-selective P2X3 receptor agonist αβmeATP. Administration of the selective P2X3 and P2X2/3 receptor antagonist A-317491 or pretreatment with oligonucleotides antisense against P2X3 receptor prevented the formalin-induced behavioral nociceptive responses during the first and second phases. Also, the co-administration of a subthreshold dose of αβmeATP with a subthreshold dose of formalin induced nociceptive behavior, which was prevented by local administration of tropisetron, HC 030031 or WAY 100, 135. These findings have demonstrated that the activation of P2X3 receptors induces inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. Also, they suggest that inflammatory nociception is modulated by the release of endogenous ATP and P2X3 receptor activation, which in turn, increases primary afferent nociceptor susceptibility to the action of inflammatory mediators via interaction with TRPA1, 5-HT3 and 5-HT1A receptors in the peripheral tissue.
Pharmacology, biochemistry, and behavior.Pharmacol Biochem Behav.2013 Nov;112:49-55. doi: 10.1016/j.pbb.2013.09.017. Epub 2013 Oct 9.
It has been described that endogenous ATP via activation of P2X3 and P2X2/3 receptors contributes to inflammatory nociception in different models, including the formalin injected in subcutaneous tissue of the rat's hind paw. In this study, we have evaluated whether TRPA1, 5-HT3 and 5-HT1A receptors,
PMID 24120766

Japanese Journal

Endogenously released 5-HT inhibits A and C fiber-evoked synaptic transmission in the rat spinal cord by the facilitation of GABA/glycine and 5-HT release via 5-HT2A and 5-HT3 receptors

Iwasaki Takeyuki,Otsuguro Ken-ichi,Kobayashi Takeshi,Ohta Toshio,Ito Shigeo
European Journal of Pharmacology 702(1-3), 149-157, 2013-02-28
… The pCA-mediated inhibition was reversed by ketanserin (a 5-HT2A receptor antagonist) and tropisetron (a 5-HT3 receptor antagonist). … in this case, the actions of 5-HT were antagonized by ketanserin, but not by tropisetron. … Furthermore, ketanserin inhibited the pCA-evoked release of gamma-aminobutyric acid (GABA) and glycine, while tropisetron inhibited the pCA-evoked release of 5-HT. …
NAID 120005228705

Antiemetic prophylaxis in thyroid surgery : a randomized, double-blind comparison of three 5-HT_3 agents

METAXARI Maria,PAPAIOANNOU Alexandra,PETROU Anastasios,CHATZIMICHALI Aikaterini,PHARMAKALIDOU Elena,ASKITOPOULOU Helen
Journal of anesthesia 25(3), 356-362, 2011-06-20
NAID 10029022996

Changes in Characteristics of the Specific Binding of [^3H]LY-278584, a 5-HT_3-Receptor Antagonist, on Differentiated NG108-15 Cells

Matsushima Kayoko,Imanishi Takashi,Asano Hajime [他],FUNAKAMI Yoshinori,WADA Tetsuyuki,ICHIDA Seiji
Journal of pharmacological sciences 113(3), 281-284, 2010-07-20
… The binding was significantly inhibited by 10 nM tropisetron, a specific 5-HT<SUB>3</SUB>–receptor antagonist, but not by any other types of 5-HT–receptor antagonists. …
NAID 10029889466

Related Pictures

★リンクテーブル★

リンク元	「セロトニン受容体」「トロピセトロン」
拡張検索	「tropisetron hydrochloride」

「セロトニン受容体」

Tropisetron
Systematic (IUPAC) name
	(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl 1methyl-indole-3-carboxylate
Clinical data
Trade names	Navoban
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	B3 (AU)
Legal status	Prescription Only (S4) (AU) POM (UK)
Routes	Oral, IV
Pharmacokinetic data
Bioavailability	~60–80%
Protein binding	71%
Metabolism	Hepatic (CYP3A4, CYP1A2, CYP2D6)
Half-life	6–8 hours
Excretion	Renal, Fecal
Identifiers
CAS number	89565-68-4
ATC code	A04AA03
PubChem	CID 72165
IUPHAR ligand	260
ChemSpider	16736476
UNII	6I819NIK1W
KEGG	D02130
ChEMBL	CHEMBL496980
Synonyms	ICS 205-930
Chemical data
Formula	C17H20N2O2
Mol. mass	284.353 g/mol
	SMILES CN4[C@@H]1CC[C@H]4C[C@H](C1)OC(=O)c3cnc2ccccc23;
	InChI InChI=1S/C17H20N2O2/c1-19-11-6-7-12(19)9-13(8-11)21-17(20)15-10-18-16-5-3-2-4-14(15)16/h2-5,10-13,18H,6-9H2,1H3/t11-,12+,13+ ; Key:ZNRGQMMCGHDTEI-ITGUQSILSA-N ;
(what is this?) (verify)

　　[★]

英: serotonin receptor
同: 5-HT受容体
関: セロトニン

セロトニン受容体 (GOO.300)

サブタイプ	シグナル	局在	機能	生体反応	選択的作動薬	選択的阻害薬
5-HT_1A	AC↓	縫線核海馬	自己受容体		8-OH-DPAT tandospirone
5-HT_1B	AC↓	鉤状回黒質	自己受容体
5-HT_1C	AC↓	脳血管	血管収縮
5-HT_1D	AC↓	皮質線条体	-		sumatriptan
5-HT_1E	AC↓	脳および末梢	-
5-HT_2A	PLC↑	血小板平滑筋大脳皮質	血小板凝集収縮神経興奮		α-methtl-5-HT, DOI	スピペロン ketanserin
5-HT_2B	PLC↑	胃底	収縮		α-methtl-5-HT, DOI
5-HT_2C	PLC↑	脈絡叢	-		α-methtl-5-HT, DOI
5-HT₃	ion channel	末梢神経	神経興奮		2-methyl-5-HT	ondansetron tropisetron
		腸神経細胞		嘔吐
		最後野		嘔吐
5-HT₄	AC↑	胃腸管	神経興奮		renzapride
5-HT₄	AC↑	海馬	神経興奮	認知	renzapride
5-HT_5A	AC↓
5-HT_5B	?	海馬	？
5-HT₆	AC↑	線条体	？
5-HT₇	AC↑	脳下垂体小腸	？

5-HT₃受容体はリガンドの結合により開閉してNa+, K+の等価に関わる。ニコチン性受容体に似ている。(GOO.299)

セロトニン受容体

5-HT₁受容体

5-HT_1A

リガンドの結合に共役してK+チャネルを開口→過分極→電位依存性カルシウムチャネルを抑制
脳幹の縫線核、に局在

鎮静作用をしめすセロトニン作動性ニューロンが存在

somatodendritic 5-HT_1A autoreceptors descrease raphe cell fireing when activated by 5-HT released from axon collaterals of the same or adjacent neurons. (GOO.301)