Trospium Chloride

Trospium Chloride is a competitive muscarinic cholinergic receptor antagonist.Target: mAChRTrospium chloride is an antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Trospium has pharmacologic properties that are distinct from other antimuscarinic agents [1]. After oral administration, absorption of the hydrophilic trospium chloride is slow and incomplete. Peak plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4-5 hours after administration of a 20 mg immediate-release preparation. The mean bioavailability is approximately 10% and decreases by concomitant food intake (to a mean of 26% of the fasting area under the plasma concentration-time curve [AUC]). Trospium chloride displays dose proportional increases in AUC and Cmax after a single dose within the clinically relevant dose range (20-60 mg). The mean volume of distribution is approximately 350-800 L [2].

Signaling Pathways >> GPCR/G Protein >> mAChR

Signaling Pathways >> Neuronal Signaling >> mAChR

Research Areas >> Neurological Disease

[1]. Staskin, D.R., Trospium chloride: Distinct among other anticholinergic agents available for the treatment of overactive bladder. Urol Clin North Am, 2006. 33(4): p. 465-73, viii.

[2]. Doroshyenko, O., et al., Clinical pharmacokinetics of trospium chloride. Clin Pharmacokinet, 2005. 44(7): p. 701-20.

Carbachol | Darifenacin HBr | Arecoline hydrobromide | Pirenzepine, Dihydrochloride | Glycopyrrolate | Imidafenacin | Benztropine Mesylate | Xanomeline oxalate | Batefenterol | Bethanechol chloride | Cevimeline hydrochloride hemihydrate | Otilonium Bromide | solifenacin | VU0467154 | Anisodamine

MOLECULAR FORMULA :

C25-H30-N-O3.Cl

MOLECULAR WEIGHT :

428.01

WISWESSER LINE NOTATION :

T56 A AKTJ GQ A-& AT5KTJ &G

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

2571 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Autonomic Nervous System - parasympatholytic Cardiac - pulse rate increase, without fall in BP

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 43,461,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1510 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

97700 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

707 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15500 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraduodenal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 25,1037,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

812 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

203 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

11200 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - nausea or vomiting

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

3200 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - altered sleep time (including change in righting reflex)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15240 mg/kg/30D-C

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes Gastrointestinal - other changes Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3822 mg/kg/13W-C

TOXIC EFFECTS :

Liver - other changes Endocrine - other changes Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

246 mg/kg/30D-C

TOXIC EFFECTS :

Endocrine - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

315 mg/kg/30D-C

TOXIC EFFECTS :

Cardiac - other changes Lungs, Thorax, or Respiration - other changes Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

1560 mg/kg/13W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,199,1974