Zatosetron

Zatosetron
Clinical data
ATC code	none;
Identifiers
	IUPAC name 5-chloro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-1-benzofuran-7-carboxamide;
CAS Number	123482-22-4 ;
PubChem CID	60763;
ChemSpider	54761 ;
UNII	901MC95XSB;
CompTox Dashboard (EPA)	DTXSID8043997 ;
Chemical and physical data
Formula	C19H25ClN2O2
Molar mass	348.867 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1(CC2=C(O1)C(=CC(=C2)Cl)C(=O)NC3CC4CCC(C3)N4C)C;
	InChI InChI=1S/C19H25ClN2O2/c1-19(2)10-11-6-12(20)7-16(17(11)24-19)18(23)21-13-8-14-4-5-15(9-13)22(14)3/h6-7,13-15H,4-5,8-10H2,1-3H3,(H,21,23) ; Key:SPKBYQZELVEOLL-UHFFFAOYSA-N ;
	(what is this?) (verify)

Zatosetron (LY-277,359) is a drug which acts as an antagonist at the 5HT₃ receptor^[1] It is orally active and has a long duration of action, producing antinauseant effects but without stimulating the rate of gastrointestinal transport.^[2]^[3] It is also an effective anxiolytic in both animal studies and human trials,^[4] although with some side effects at higher doses.^[5]^[6]

References

^ Cohen, ML; Bloomquist, W; Gidda, JS; Lacefield, W (1990). "LY277359 maleate: a potent and selective 5-HT3 receptor antagonist without gastroprokinetic activity". The Journal of Pharmacology and Experimental Therapeutics. 254 (1): 350–5. PMID 2366187.
^ Robertson, DW; Lacefield, WB; Bloomquist, W; Pfeifer, W; Simon, RL; Cohen, ML (1992). "Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships". Journal of Medicinal Chemistry. 35 (2): 310–9. doi:10.1021/jm00080a016. PMID 1732548.
^ Schwartz, SM; Goldberg, MJ; Gidda, JS; Cerimele, BJ (1994). "Effect of zatosetron on ipecac-induced emesis in dogs and healthy men". Journal of clinical pharmacology. 34 (3): 250–4. doi:10.1002/j.1552-4604.1994.tb03994.x. PMID 7517409.
^ Smith, WT; Londborg, PD; Blomgren, SL; Tollefson, GD; Sayler, ME (1999). "Pilot study of zatosetron (LY277359) maleate, a 5-hydroxytryptamine-3 antagonist, in the treatment of anxiety". Journal of Clinical Psychopharmacology. 19 (2): 125–31. doi:10.1097/00004714-199904000-00006. PMID 10211913.
^ Williams, PD; Calligaro, DO; Colbert, WE; Helton, DR; Shetler, T; Turk, JA; Jordan, WH (1991). "General pharmacology of a new potent 5-hydroxytryptamine antagonist". Arzneimittel-Forschung. 41 (3): 189–95. PMID 1867653.
^ Bendele, A; Means, J; Shoufler, J; Schmalz, C; Hanasono, G; Symanowski, J; Adams, E (1995). "Chronic toxicity of zatosetron, a 5-HT3 receptor antagonist, in rhesus monkeys". Drug and chemical toxicology. 18 (1): 61–82. doi:10.3109/01480549509017858. PMID 7768200.

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[1] Cohen, ML; Bloomquist, W; Gidda, JS; Lacefield, W (1990). "LY277359 maleate: a potent and selective 5-HT3 receptor antagonist without gastroprokinetic activity". The Journal of Pharmacology and Experimental Therapeutics. 254 (1): 350–5. PMID 2366187.

[2] Robertson, DW; Lacefield, WB; Bloomquist, W; Pfeifer, W; Simon, RL; Cohen, ML (1992). "Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships". Journal of Medicinal Chemistry. 35 (2): 310–9. doi:10.1021/jm00080a016. PMID 1732548.

[3] Schwartz, SM; Goldberg, MJ; Gidda, JS; Cerimele, BJ (1994). "Effect of zatosetron on ipecac-induced emesis in dogs and healthy men". Journal of clinical pharmacology. 34 (3): 250–4. doi:10.1002/j.1552-4604.1994.tb03994.x. PMID 7517409.

[4] Smith, WT; Londborg, PD; Blomgren, SL; Tollefson, GD; Sayler, ME (1999). "Pilot study of zatosetron (LY277359) maleate, a 5-hydroxytryptamine-3 antagonist, in the treatment of anxiety". Journal of Clinical Psychopharmacology. 19 (2): 125–31. doi:10.1097/00004714-199904000-00006. PMID 10211913.

[5] Williams, PD; Calligaro, DO; Colbert, WE; Helton, DR; Shetler, T; Turk, JA; Jordan, WH (1991). "General pharmacology of a new potent 5-hydroxytryptamine antagonist". Arzneimittel-Forschung. 41 (3): 189–95. PMID 1867653.

[6] Bendele, A; Means, J; Shoufler, J; Schmalz, C; Hanasono, G; Symanowski, J; Adams, E (1995). "Chronic toxicity of zatosetron, a 5-HT3 receptor antagonist, in rhesus monkeys". Drug and chemical toxicology. 18 (1): 61–82. doi:10.3109/01480549509017858. PMID 7768200.

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v t e Anxiolytics (N05B)
5-HT_1ARTooltip 5-HT1A receptor agonists	Buspirone Gepirone Tandospirone
GABA_ARTooltip GABAA receptor PAMsTooltip positive allosteric modulators	Benzodiazepines: Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam^# Ethyl loflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam^# Medazepam Nordazepam Oxazepam Pinazepam Prazepam; Others: Alpidem^‡ Barbiturates (e.g., phenobarbital) Carbamates (e.g., meprobamate) Carisoprodol Chlormezanone^‡ Ethanol (alcohol) Etifoxine
Hypnotics	Zopiclone
Gabapentinoids (α₂δ VDCC blockers)	Gabapentin Gabapentin enacarbil Phenibut Pregabalin
Antidepressants	SSRIsTooltip Selective serotonin reuptake inhibitors (e.g., escitalopram) SNRIsTooltip Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) SARIsTooltip Serotonin antagonist and reuptake inhibitors (e.g., trazodone) TCAsTooltip Tricyclic antidepressants (e.g., clomipramine^#) TeCAsTooltip Tetracyclic antidepressants (e.g., mirtazapine) MAOIsTooltip Monoamine oxidase inhibitors (e.g., phenelzine); Others: Agomelatine Bupropion Tianeptine Vilazodone Vortioxetine
Antipsychotics	Quetiapine Flupentixol
Sympatholytics (Antiadrenergics)	Alpha-1 blockers (e.g., prazosin) Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine) Beta blockers (e.g., propranolol)
Others	Benzoctamine Cycloserine Fabomotizole Hydroxyzine Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane^‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

v t e Antiemetics (A04)
5-HT₃ serotonin ion channel antagonists	Alosetron Azasetron Bemesetron Cilansetron Clozapine Dazopride Dolasetron Granisetron Lerisetron Mianserin Mirtazapine Olanzapine Ondansetron Palonosetron (+netupitant) Quetiapine Ramosetron Ricasetron Tropisetron Zatosetron
5-HT serotonin G-protein receptor antagonists	Clozapine Cyproheptadine Hydroxyzine Olanzapine Risperidone Ziprasidone
CB₁ agonists (cannabinoids)	Dronabinol Nabilone Tetrahydrocannabinol (cannabis)
D₂/D₃ antagonists	Chlorpromazine Haloperidol Hydroxyzine Metoclopramide Metopimazine Prochlorperazine Thiethylperazine Trimethobenzamide
H₁ antagonists (antihistamines)	Cyclizine Dimenhydrinate Diphenhydramine Hydroxyzine Meclizine Promethazine
mACh antagonists (anticholinergics)	Atropine Diphenhydramine Hydroxyzine (very mild) Hyoscyamine Scopolamine
NK₁ antagonists	Aprepitant Fosaprepitant Maropitant Netupitant Rolapitant
Others	Amisulpride Cerium oxalate Dexamethasone Lorazepam Midazolam Propofol

See also

References