Zatosetron (maleate)

Zatosetron maleate is a potent and selective 5HT3 receptor antagonist.

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Research Areas >> Neurological Disease

5HT3 receptor[1]

Acute administration of 0.1 (n=21) and 0.3 (n=5) mg/kg Zatosetron maleate (Zatosetron) in male rats, but not 0.01, 0.05, 1.0 or 10 mg/kg (n=5, 3, 6 and 4, respectively) Zatosetron maleate or saline (n=5), leads to a significant reduction in the number of spontaneously active A10 dopamine cells. The number of spontaneously active A10 dopamine cells is not significantly different from 30 to 60 min post i.p. Zatosetron maleate (0.1 mg/kg) administration, shows a significant decrease by 60 to 90 min (0.65±0.11, P=0.03, n=5), a larger decrease by 90 to120 min (0.53±0.08, P=0.004, n=5) and remains at this significantly decreased level from 2 to 3 h (0.50+0.05, P=0.0004, n=5). Single-unit recordings show that Zatosetron maleate inhibits the activity of A10 dopamine cells following i.v. administration (ED50=0.12 mg/kg, n=8). Chronic administration of 0.1 mg/kg (n=16) Zatosetron maleate, but not 0.01, 1.0 or 10 mg/kg (n=4, 8 and 7, respectively) Zatosetron maleate or saline (n=5), leads to a significant reduction in the number of spontaneously active A10 dopamine cells[2].

Male rats are used and Zatosetron maleate (Zatosetron) is prepared as an aqueous solution. Acutely treated animals receive i.p. injections of Zatosetron maleate or saline 2 h before electrophysiological recordings; Chronically treated animals receive injections (i.p.) of Zatosetron maleate or saline once daily for 21 days, and receive their last injection 2 h before electrophysiological recordings. After completion of nine tracks, some animals are administered either apomorphine HCI (0.14 or 0.01 mg/kg i.v.) or haloperidol (0.1 mg/kg i.v.) and the number of dopamine cells is then counted in three additional tracks[2].

[1]. Robertson DW, et al. Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. J Med Chem. 1992 Jan 24;35(2):310-9.

[2]. Rasmussen K, et al. The 5-HT3 receptor antagonist zatosetron decreases the number of spontaneously active A10 dopamine neurons. Eur J Pharmacol. 1991 Nov 19; 205 (1):113-6.

Harmine | Pimavanserin | Serotonin hydrochloride | Sodium Ferulate | Thioridazine hydrochloride | Brexpiprazole | Risperidone | TG6-10-1 | Cariprazine | Quetiapine | SERTINDOLE | Alprenolol hydrochloride | B-HT 920 | Ketanserin | Palonosetron hydrochloride

MOLECULAR WEIGHT :

464.99

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

38220 mg/kg/1Y-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 22,494,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

3650 mg/kg/1Y-I

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects

REFERENCE :

DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 18,61,1995