Granisetron hydrochloride

Granisetron Hcl(BRL 43694A) is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy.IC50 Value: 17uM (GR reduced 5-HT-evoked contractions) [1]Target: 5-HT3 receptorin vitro: In rat forestomach GR reduced 5-HT-evoked contractions at IC50 17 /- 6 uM. In isolated rabbit heart, GR 0.003-0.03 nM dose-dependently reduced s-HT tachycardia; at high levels GR reduced submaximal and maximal responses to 5-HT [1].in vivo: Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. Granisetron increased PGE(2) level at a lower dose (50 microg/pouch) but higher doses (100 and 200 microg/pouch) inhibited the release. At the same time, TNFalpha production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion [2]. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation [3].Clinical trial: Effect of External Heat on a Transdermal Granisetron Patch in Pharmacokinetics (PK) of Healthy Subjects. Phase 1

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

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

Research Areas >> Neurological Disease

[1]. Sanger GJ, Nelson DR. Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron). Eur J Pharmacol. 1989 Jan 10;159(2):113-24.

[2]. Maleki-Dizaji N, Eteraf-Oskouei T, Fakhrjou A, The effects of 5HT3 receptor antagonist granisetron on inflammatory parameters and angiogenesis in the air-pouch model of inflammation. Int Immunopharmacol. 2010 Sep;10(9):1010-6.

[3]. Boccia RV, Gordan LN, Clark G, Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III

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 FORMULA :

C18-H24-N4-O.Cl-H

MOLECULAR WEIGHT :

348.92

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

350 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

14 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

350 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

17 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

3 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - tremor Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4500 mg/kg/30D-I

TOXIC EFFECTS :

Liver - changes in liver weight Blood - changes in leukocyte (WBC) count Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

18200 mg/kg/26W-I

TOXIC EFFECTS :

Liver - changes in liver weight Blood - changes in platelet count Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

325 mg/kg/30D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

52 mg/kg

SEX/DURATION :

male 10 week(s) pre-mating female 2 week(s) pre-mating - 19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

MUTATION DATA

TYPE OF TEST :

Cytogenetic analysis

TEST SYSTEM :

Human Lymphocyte

DOSE/DURATION :

1500 mg/L

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 24,6795,1990