Pilsicainide hydrochloride

Names

[ Name ]:
Pilsicainide hydrochloride

[Synonym ]:
N-(2,6-Dimethylphenyl)-2-(tetrahydro-1H-pyrrolizin-7a(5H)-yl)acetamide hydrochloride hydrate
Sunrythm
Pilsicainide HCl
1H-Pyrrolizine-7a(5H)-acetamide,N-(2,6-dimethylphenyl)tetrahydro-,monohydrochloride
Sunrythm(R)
N-(2,6-dimethylphenyl)-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-yl)acetamide hydrochloride
Pilsicainide hydrochloride
N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate
1H-Pyrrolizine-7a(5H)-acetamide, N-(2,6-dimethylphenyl)tetrahydro-, hydrochloride, hydrate (1:1:1)
Tetrahydro-N-(2,6-dimethylphenyl)-1H-pyrrolizine-7a(5H)-acetamide hydrochloride hemihydrate
SUN 1165
N-(2,6-Dimethylphenyl)-1H-pyrrolizine-8-acetamide hydrochloride
Pilsicainide Hydrochloride Hemihydrate
N-(2,6-Dimethylphenyl)-8-pyrrolizidineacetamide monohydrochloride
1H-Pyrrolizine-8-acetamide,hexahydro-N-(2,6-dimethylphenyl)-,hydrochloride

Biological Activity

[Description]:

Pilsicainide hydrochloride (SUN-1165) is an orally active sodium channel blocker and potent class Ic antiarrhythmic agent[1][2].

[Related Catalog]:

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

Research Areas >> Cardiovascular Disease

[In Vitro]

Pilsicainide hydrochloride (SUN-1165) (10-200 μg/mL) decreases peak amplitude of the net inward current in a dose-dependent manner with an IC50 of 29.2 ± 22.9 μg/mL in levo-thyroxine (T4)-treated rat atrial cells[1].

[In Vivo]

Pilsicainide hydrochloride (SUN-1165) (2 mg/kg; i.v.; once) decreases the conduction velocity in T4-treated rat atrium by decreasing the Max dV/dt and net inward current[1]. Animal Model: Male Sprague-Dawley (SD) rats weighing from 200 to 220 g, with levo-thyroxine (T4) treatment[1] Dosage: 2 mg/kg Administration: Bolus injection into right external carotid vein within 2 minutes, once Result: Result: the QT interval was significantly elongated at 15 and 60 minutes after administration. P wave and QRS complex durations were significantly shortened. Markedly decreased action potential amplitudes (APA) and Max dV/dt, and significantly lengthened the action potential durations.

[References]

[1]. Yamakawa M, et al. Effect of sodium channel blocker, pilsicainide hydrochloride, on net inward current of atrial myocytes in thyroid hormone toxicosis rats. Thyroid. 2005 Jul;15(7):653-9.

[2]. Plosker GL. Pilsicainide. Drugs. 2010 Mar 5;70(4):455-67.

Chemical & Physical Properties

[ Boiling Point ]:
416.9ºC at 760 mmHg

[ Melting Point ]:
212-214°

[ Molecular Formula ]:
C₁₇H₂₄N₂O

[ Molecular Weight ]:
326.862

[ Flash Point ]:
205.9ºC

[ Exact Mass ]:
326.176117

[ PSA ]:
32.34000

[ LogP ]:
3.27130

[ Storage condition ]:
2-8°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UY7758200

CAS REGISTRY NUMBER :: 88069-49-2

LAST UPDATED :: 199712

DATA ITEMS CITED :: 14

MOLECULAR FORMULA :: C17-H24-N2-O.Cl-H.1/2H2-O

MOLECULAR WEIGHT :: 317.86

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 :: 255 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 depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,457,1991

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 105 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 depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,457,1991

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18 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 depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,457,1991

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 175 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 depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,457,1991

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 85 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 depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,457,1991

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 410 mg/kg

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

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 28,714,1985

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 depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,457,1991

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 50 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - tremor Behavioral - changes in motor activity (specific assay)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 38,1398,1988

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 18 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Cardiac - other changes 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: 42,461,1991

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 87 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - tremor Behavioral - changes in motor activity (specific assay)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 38,1398,1988 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14560 mg/kg/13W-I

TOXIC EFFECTS :: Behavioral - food intake (animal) 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: 42,469,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 252 mg/kg/4W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - respiratory stimulation 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: 54,1,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2730 mg/kg/13W-I

TOXIC EFFECTS :: Cardiac - 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: 42,485,1991

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 168 mg/kg/4W-I

TOXIC EFFECTS :: 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: 54,1,1997

Safety Information

[ Hazard Codes ]:
Xi

[ HS Code ]:
2933990090

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%