Verapamil

Names

[ CAS No. ]:
52-53-9

[ Name ]:
Verapamil

[Synonym ]:
eronitrile
aleronitrile
2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
EINECS 200-145-1
5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile
R,S-Verapamil
a-((N-Methyl-N-homoveratryl)-g-aminopropyl)-3,4-dimethoxyphenylacetonitrile
Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)-
Dilacoran
Benzeneacetonitrile, α-(3-((2-(3,4-dimethoxyphenyl)ethyl)methylamino)propyl)-3,4-dimethoxy-α-(1-methylethyl)-, (±)-
VPL
Vasolan
a-Isopropyl-a-[(N-methyl-N-homoveratryl)-g-aminopropyl]-3,4-dimethoxyphenylacetonitrile
Benzeneacetonitrile, α-(3-((2-(3,4-dimethoxyphenyl)ethyl)methylamino)propyl)-3,4-dimethoxy-α-(1-methylethyl)-
Verapamil
2-isopropyl
MFCD00056240
(±)-Verapamil
D-365
CP 16533-1
2-(3,4-Dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-isopropylpentanenitrile
dl-Verapamil
a-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-a-(1-methylethyl)benzeneacetonitrile
benzeneacetonitrile, a-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-a-(1-methylethyl)-

Biological Activity

[Description]:

Verapamil ((±)-Verapamil) is a calcium channel blocker and a potent and orally active first-generation P-glycoprotein (P-gp) inhibitor. Verapamil also inhibits CYP3A4. Verapamil has the potential for high blood pressure, heart arrhythmias and angina treatment[1][2][3].

[Related Catalog]:

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

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

Research Areas >> Metabolic Disease

[Target]

Calcium channel[1] Permeability-glycoprotein (P-gp)[1] CYP3A4[1]

[In Vitro]

The EverFluor FL Verapamil (EFV) uptake by TR-iBRB2 cells is inhibited by cationic drugs, and inhibits by verapamil in a concentration-dependent manner with an IC50 of 98.0 μM[4].

[In Vivo]

Intravenous Verapamil is highly effective in the termination of paroxysmal reciprocating atrioventricular tachycardia, whether associated with preexcitation or involving the atrioventricular node alone[2]. Given orally it is useful for the prophylaxis of atrioventricular reentry tachycardia, and also in modulating the atrioventricular nodal response in atrial fibrillation[2].

[References]

[1]. Gowarty JL, et al. Verapamil as a culprit of palbociclib toxicity. J Oncol Pharm Pract. 2019 Apr;25(3):743-746.

[2]. Krikler DM. Verapamil in arrhythmia. Br J Clin Pharmacol. 1986;21 Suppl 2:183S-189S.

[3]. Rehnqvist N,et al. Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS). Eur Heart J. 1996 Jan;17(1):76-81.

[4]. Kubo Y, et al. Blood-to-Retina Transport of Fluorescence-Labeled Verapamil at the Blood-Retinal Barrier. Pharm Res. 2018 Mar 12;35(5):93.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
586.2±50.0 °C at 760 mmHg

[ Melting Point ]:
25°C

[ Molecular Formula ]:
C₂₇H₃₈N₂O₄

[ Molecular Weight ]:
454.602

[ Flash Point ]:
308.3±30.1 °C

[ Exact Mass ]:
454.283173

[ PSA ]:
63.95000

[ LogP ]:
3.90

[ Vapour Pressure ]:
0.0±1.6 mmHg at 25°C

[ Index of Refraction ]:
1.526

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YV8300000

CHEMICAL NAME :: Valeronitrile, 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimeth oxyphenyl)-2-isopropy l-

CAS REGISTRY NUMBER :: 52-53-9

LAST UPDATED :: 199801

DATA ITEMS CITED :: 19

MOLECULAR FORMULA :: C27-H38-N2-O4

MOLECULAR WEIGHT :: 454.67

WISWESSER LINE NOTATION :: 1OR BO1 DXCN&Y1&1&3N1&2R CO1 DO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 80 mg/kg

TOXIC EFFECTS :: Behavioral - coma Cardiac - pulse rate increase, without fall in BP Vascular - BP lowering not characterized in autonomic section

REFERENCE :: HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990- Volume(issue)/page/year: 16,35,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 46 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Cardiac - EKG changes not diagnostic of specified effects Vascular - BP lowering not characterized in autonomic section

REFERENCE :: CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 17,395,1980

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 2 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified Cardiac - other changes Vascular - BP lowering not characterized in autonomic section

REFERENCE :: CHETBF Chest. (American College of Chest Physicians, 911 Busse Hwy, Park Ridge, IL 60068) V.57- 1970- Volume(issue)/page/year: 75,200,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 64 mg/kg

TOXIC EFFECTS :: Cardiac - pulse rate Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section

REFERENCE :: BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,1127,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 48 mg/kg/2W-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), diffuse

REFERENCE :: NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 306,612,1982

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 83 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Cardiac - cardiomyopathy including infarction Vascular - BP lowering not characterized in autonomic section

REFERENCE :: AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 7,624,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 3429 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Cardiac - pulse rate Lungs, Thorax, or Respiration - acute pulmonary edema

REFERENCE :: CCMDC7 Critical Care Medicine. (Williams & Wilkins, 428 E. Preston Street, Baltimore, MD 21202) V.1- 1973- Volume(issue)/page/year: 19,436,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 1429 ug/kg/5M-C

TOXIC EFFECTS :: Cardiac - pulse rate Lungs, Thorax, or Respiration - cyanosis Skin and Appendages - sweating

REFERENCE :: NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 306,238,1982

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 71 ug/kg

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 111,622,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 250 ug/kg/5M-C

TOXIC EFFECTS :: Cardiac - arrhythmias (including changes in conduction)

REFERENCE :: AHJOA2 American Heart Journal. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1925- Volume(issue)/page/year: 106,145,1983

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 163 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique. (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France) V.9- 1974- Volume(issue)/page/year: 25,351,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 7250 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PCJOAU Pharmaceutical Chemistry Journal (English Translation). Translation of KHFZAN. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No.1- 1967- Volume(issue)/page/year: 22,123,1988

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 130 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 54(2),40,1991

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 43 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JDGRAX Journal of Drug Research. (National Organization for Drug Research and Control, POB 29, Cairo, Egypt) V.2- 1969- Volume(issue)/page/year: 15(1-2),121,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 30770 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JPPMAB Journal of Pharmacy and Pharmacology. (Pharmaceutical Soc. of Great Britain, 1 Lambeth High St., London SEI 7JN, UK) V.1- 1949- Volume(issue)/page/year: 34,329,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1520 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EJTXAZ European Journal of Toxicology and Environmental Hygiene. (Paris, France) V.7-9, 1974-76. For publisher information, see TOERD9. Volume(issue)/page/year: 8,188,1975 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 51 mg/kg

SEX/DURATION :: male 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - breast development

REFERENCE :: MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 161,328,1994

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 60 mg/kg

SEX/DURATION :: female 10-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

REFERENCE :: REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 11,207,1997 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4662 No. of Facilities: 65 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 14268 (estimated) No. of Female Employees: 7372 (estimated)

Safety Information

[ Hazard Codes ]:
C

[ Risk Phrases ]:
R14:Reacts violently with water. R34:Causes burns. R37:Irritating to the respiratory system.

[ Safety Phrases ]:
S26-S36/37/39-S43-S45

[ RIDADR ]:
UN 1939 8/PG 2

[ WGK Germany ]:
3

[ Packaging Group ]:
II

[ Hazard Class ]:
8

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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