Verapamil HCl

Verapamil hydrochloride is a calcium channel antagonist.

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cardiovascular Disease

Calcium channel[1]

Verapamil (hydrochloride) is an L-type calcium channel antagonist. The combination of Bortezomib and Verapamil (70 µM) markedly declines the viability of the JK-6L, RPMI 8226, and ARH-77 cell lines after 16 hours of culture[1]. The enzyme hydrolase activity of recombinant human carboxylesterase (CES2) is substantially inhibited by Verapamil with Ki of 3.84±0.99μM[2].

Verapamil, a calcium channel antagonist, is injected i.v. into a femoral vein prior to ischemia. Verapamil (1 mg/kg) significantly decreases the incidence of ventricular arrhythmias including premature ventricular contractions (PVC), ventricular tachycardia (VT) and ventricular fibrillation (VF) for 45-min coronary artery occlusion. Total arrhythmia scores are significantly increased when the heart is subjected to ischemia (P<0.01 vs. sham). Verapamil (1 mg/kg) significantly prevented the enhancement of total arrhythmia scores induced by ischemia (P<0.01 vs. ischemia). Results indicate that Verapamil exerts an anti-arrhythmic property[3].

Cells (1×105) are treated with 10 nM Bortezomib and/or 70 µM Verapamil for 16 hours and incubated for another 4 hours with Alamar-Blue. Activity of the mitochondrial dehydrogenase results in conversion of the coloring, which is followed by measurement of the absorption using a spectrophotometer[1].

Rats[3] Adult male Sprague-Dawley (SD) rats (250−350 g) are used. Verapamil (1 mg/kg) is injected i.v. into a femoral vein 10 min prior to ischemia. A sham group undergoes the same surgical procedures, except the suture underneath the LAD is left untied. In another series of experiment, arrhythmia is induced by Bay K8644, an L-type calcium channel agonist, at a dose of 0.1 mg/kg given i.v. into the FV. Verapamil (1 mg/kg) is administered 10 min prior to Bay K8644. All injections are performed within 30 sec.

[1]. Meister S, et al. Calcium channel blocker Verapamil enhances endoplasmic reticulum stress and cell death induced by proteasome inhibition in myeloma cells. Neoplasia. 2010 Jul;12(7):550-61.

[2]. Yanjiao X, et al. Evaluation of the inhibitory effects of antihypertensive drugs on human carboxylesterase in vitro. Drug Metab Pharmacokinet. 2013;28(6):468-74.

[3]. Zhou P, et al. Anti-arrhythmic effect of Verapamil is accompanied by preservation of cx43 protein in rat heart. PLoS One. 2013 Aug 12;8(8):e71567.

Neomycin sulfate | Nifedipine | Acetylcholine chloride | Ionomycin | (S)-(-)-Bay K 8644 | Nimodipine | Mibefradil dihydrochloride | Levetiracetam | CDN 1163 | Dantrolene sodium | Thapsigargin | Flufenamic Acid | ABT 639 | Ranolazine dihydrochloride | Cromolyn (sodium)

MOLECULAR FORMULA :

C27-H38-N2-O4.Cl-H

MOLECULAR WEIGHT :

491.13

WISWESSER LINE NOTATION :

1OR BO1 DXCNY1&1&3N1&2R CO1 DO1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

96 mg/kg

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - acute pulmonary edema

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

72 mg/kg/14H-I

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects Cardiac - pulse rate Vascular - BP lowering not characterized in autonomic section

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

58 mg/kg

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - acute pulmonary edema

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

80 mg/kg

TOXIC EFFECTS :

Behavioral - coma Cardiac - pulse rate Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

89 mg/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Vascular - BP lowering not characterized in autonomic section Nutritional and Gross Metabolic - changes in calcium

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

14400 ug/kg

TOXIC EFFECTS :

Vascular - regional or general arteriolar constriction

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3429 ug/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Gastrointestinal - necrotic changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

135 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - coma Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

26 mg/kg

TOXIC EFFECTS :

Cardiac - pulse rate Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

143 ug/kg/4H-C

TOXIC EFFECTS :

Vascular - BP lowering not characterized in autonomic section

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

68571 mg/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Cardiac - pulse rate Vascular - regional or general arteriolar or venous dilation

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

71 ug/kg/5M-C

TOXIC EFFECTS :

Behavioral - excitement Cardiac - arrhythmias (including changes in conduction) Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

1026 ug/kg

TOXIC EFFECTS :

Cardiac - pulse rate Vascular - BP lowering not characterized in autonomic section

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

200 ug/kg/15S-C

TOXIC EFFECTS :

Cardiac - cardiomyopathy including infarction Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

256 ug/kg/1H-I

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

108 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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

60 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 :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

107 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 :

16 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 :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

47 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 :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

163 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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

41 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 :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

68 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 :

5795 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

45 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 :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>400 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 :

Intramuscular

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

25 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 :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

140 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

128 mg/kg

SEX/DURATION :

male 28 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - impotence

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

264 mg/kg

SEX/DURATION :

female 1-22 day(s) after conception lactating female 22 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - blood and lymphatic systems (including spleen and marrow)

MUTATION DATA

TYPE OF TEST :

Cytogenetic analysis

TEST SYSTEM :

Human Lymphocyte

DOSE/DURATION :

30 umol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 244,135,1990 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5040 No. of Facilities: 174 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 3974 (estimated) No. of Female Employees: 2638 (estimated)