RTECS:NW8450000 The Registry of Toxic Effects of Chemical Substances

Isoquinoline, 1 - ( (3,4 - dimethoxyphenyl) methyl) - 6,7 - dimethoxy -

RTECS #: NW8450000

CAS #: 58-74-2

UPDATE: May 2008 MW: 339.42 MF: C₂₀H₂₁NO₄

NOTE:

TOXICITY DATA HAVE NOT BEEN EVALUATED. OMISSION OF A SUBSTANCE OR NOTATION DOES NOT IMPLY ANY RELIEF FROM REGULATORY RESPONSIBILITY.

TABLE OF CONTENTS:

SYNONYMS:

MUTATION DATA:

ACUTE TOXICITY DATA:

REVIEWS:

NIOSH DOCUMENTATION AND SURVEILLANCE:

REFERENCES:

SYNONYMS:

1 - ( (3,4 - Dimethoxyphenyl) methyl) - 6,7 - dimethoxyisoquinoline

6,7 - Dimethoxy - 1 - veratrylisoquinoline

Isoquinoline, 6,7 - dimethoxy - 1 - veratryl -

Papanerine

Papaverina (Italian)

Papaverine

SKIN AND EYE IRRITATION DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
N/R
N/R N/R N/R

MUTATION DATA AND REFERENCES:
SYSTEM TEST ROUTE/
ORGANISM/
TISSUE DOSE REFERENCE
other mutation test systems mouse other cell types 100 痠ol/L JIDEAE 66,313,1976

REPRODUCTIVE EFFECTS DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
N/R
N/R N/R N/R

TUMORIGENIC DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
N/R
N/R N/R N/R

ACUTE TOXICITY DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
intradermal
mouse lethal dose (50 percent kill): 150 mg/kg Behavioral: Excitement

Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea AIPTAK 59,149,1938
intramuscular
man lowest published toxic dose: 1,143 痢/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Coma EJCPAS 33,651,1988
intramuscular
mouse lethal dose (50 percent kill): 175 mg/kg N/R AITEAT 15,415,1967
intraperitoneal
mouse lethal dose (50 percent kill): 91 mg/kg N/R USXXAM #4738965
intraperitoneal
rat lethal dose (50 percent kill): 59,600 痢/kg N/R ARZNAD 20,1338,1970
intravenous
mouse lethal dose (50 percent kill): 25 mg/kg Behavioral: Excitement

Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea AIPTAK 59,149,1938
intravenous
rat lethal dose (50 percent kill): 13,300 痢/kg N/R ARZNAD 26,2172,1976
intravenous
rat lowest published toxic dose: 5 mg/kg Vascular: Measurement of regional blood flow JCPCDT 35,630,2000
intravenous
rat lowest published toxic dose: 1.697 mg/kg Vascular: BP lowering not characterized in autonomic section JMCMAR 44,2950,2001
intravenous
rabbit lethal dose (50 percent kill): 25 mg/kg Behavioral: Excitement

Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea AIPTAK 59,149,1938
intravenous
rabbit lowest published toxic dose: 17.8 mg/kg Blood: Change in clotting factors FATOAO 49,48,1986
oral
man lowest published lethal dose: 114.3 mg/kg Behavioral: Convulsions or effect on seizure threshold

Behavioral: Coma

Gastrointestinal: Nausea or vomiting AJEMEN 21,245,2003
oral
mouse lethal dose (50 percent kill): 162 mg/kg N/R THERAP 14,731,1959
oral
rat lethal dose (50 percent kill): 325 mg/kg N/R ARZNAD 20,1338,1970
oral
rabbit lowest published lethal dose: 190 mg/kg N/R HBAMAK 4,1289,1935
parenteral
frog lowest published lethal dose: 225 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Cardiac: Pulse rate decreased with fall in BP

Gastrointestinal: Nausea or vomiting JPETAB 25,35,1925
subcutaneous
cat lowest published lethal dose: 120 mg/kg N/R FDWU -,-,1931
subcutaneous
dog lowest published lethal dose: 120 mg/kg N/R FDWU -,-,1931
subcutaneous
frog lowest published lethal dose: 140 mg/kg N/R HBAMAK 4,1289,1935
subcutaneous
mouse lethal dose (50 percent kill): 170 mg/kg N/R AEPPAE 227,129,1955
subcutaneous
pigeon lowest published lethal dose: 150 mg/kg N/R FDWU -,-,1931
subcutaneous
rat lethal dose (50 percent kill): 151 mg/kg N/R ARZNAD 20,1338,1970
subcutaneous
rabbit lowest published lethal dose: 250 mg/kg N/R HBAMAK 4,1289,1935

OTHER MULTIPLE DOSE DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
N/R
N/R N/R N/R

REVIEWS:
ORGANIZATION STANDARD
REFERENCE**

TOXICOLOGY REVIEW
DIMON* 39,678,1993

STANDARDS AND REGULATIONS:
ORGANIZATION STANDARD
REFERENCE

N/R N/R N/R

NIOSH DOCUMENTATION AND SURVEILLANCE:
ORGANIZATION STANDARD or SURVEY
REFERENCE

National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X4373;
Number of Industries 1;
Total Number of Facilities 17;
Number of Occupations 2;
Total Number of Employees Exposed 563;
Total Number of Female Employees Exposed 481

STATUS IN FEDERAL AGENCIES:
ORGANIZATION
REFERENCE

N/R

REFERENCES:
CODEN
REFERENCE

AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC.
AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898-
AITEAT Archivum Immunologiae et Therapiae Experimentalis. (Ars Polona, POB 1001, 00-068 Warsaw 1, Poland) V.10- 1962-
AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
DIMON* Disease-a Month (Chicago : Year Book Publishers) V. 24- 1978-
EJCPAS European Journal of Clinical Pharmacology. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.3- 1970-
FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939-
FDWU** "Ueber die Wirkung Verschiedener Gifte Auf Vogel, Dissertation," Forchheimer, L., Pharmakologischen Institut der Universitat Wurzburg, Fed. Rep. Ger., 1931
HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.)
JCPCDT Journal of Cardiovascular Pharmacology. (Raven Press, 1140 Ave. of the Americas, New York, NY 10036) V.1- 1979-
JIDEAE Journal of Investigative Dermatology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1938-
JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946-
USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231)

Used as a cerebral vasodilator and smooth muscle relaxant

RTECS Compound Description:
   Drug
   Mutagen
   Human Data

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SYNONYMS:
1 - ( (3,4 - Dimethoxyphenyl) methyl) - 6,7 - dimethoxyisoquinoline 6,7 - Dimethoxy - 1 - veratrylisoquinoline Isoquinoline, 6,7 - dimethoxy - 1 - veratryl -	Papanerine Papaverina (Italian) Papaverine

SKIN AND EYE IRRITATION DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
N/R	N/R	N/R	N/R

MUTATION DATA AND REFERENCES:
SYSTEM TEST	ROUTE/ ORGANISM/ TISSUE	DOSE	REFERENCE
other mutation test systems	mouse other cell types	100 痠ol/L	JIDEAE 66,313,1976

REPRODUCTIVE EFFECTS DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
N/R	N/R	N/R	N/R

TUMORIGENIC DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
N/R	N/R	N/R	N/R

ACUTE TOXICITY DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
intradermal mouse	lethal dose (50 percent kill): 150 mg/kg	Behavioral: Excitement Behavioral: Ataxia Lung, Thorax, or Respiration: Dyspnea	AIPTAK 59,149,1938
intramuscular man	lowest published toxic dose: 1,143 痢/kg	Behavioral: Somnolence (general depressed activity) Behavioral: Coma	EJCPAS 33,651,1988
intramuscular mouse	lethal dose (50 percent kill): 175 mg/kg	N/R	AITEAT 15,415,1967
intraperitoneal mouse	lethal dose (50 percent kill): 91 mg/kg	N/R	USXXAM #4738965
intraperitoneal rat	lethal dose (50 percent kill): 59,600 痢/kg	N/R	ARZNAD 20,1338,1970
intravenous mouse	lethal dose (50 percent kill): 25 mg/kg	Behavioral: Excitement Behavioral: Ataxia Lung, Thorax, or Respiration: Dyspnea	AIPTAK 59,149,1938
intravenous rat	lethal dose (50 percent kill): 13,300 痢/kg	N/R	ARZNAD 26,2172,1976
intravenous rat	lowest published toxic dose: 5 mg/kg	Vascular: Measurement of regional blood flow	JCPCDT 35,630,2000
intravenous rat	lowest published toxic dose: 1.697 mg/kg	Vascular: BP lowering not characterized in autonomic section	JMCMAR 44,2950,2001
intravenous rabbit	lethal dose (50 percent kill): 25 mg/kg	Behavioral: Excitement Behavioral: Ataxia Lung, Thorax, or Respiration: Dyspnea	AIPTAK 59,149,1938
intravenous rabbit	lowest published toxic dose: 17.8 mg/kg	Blood: Change in clotting factors	FATOAO 49,48,1986
oral man	lowest published lethal dose: 114.3 mg/kg	Behavioral: Convulsions or effect on seizure threshold Behavioral: Coma Gastrointestinal: Nausea or vomiting	AJEMEN 21,245,2003
oral mouse	lethal dose (50 percent kill): 162 mg/kg	N/R	THERAP 14,731,1959
oral rat	lethal dose (50 percent kill): 325 mg/kg	N/R	ARZNAD 20,1338,1970
oral rabbit	lowest published lethal dose: 190 mg/kg	N/R	HBAMAK 4,1289,1935
parenteral frog	lowest published lethal dose: 225 mg/kg	Behavioral: Altered sleep time (including change in righting reflex) Cardiac: Pulse rate decreased with fall in BP Gastrointestinal: Nausea or vomiting	JPETAB 25,35,1925
subcutaneous cat	lowest published lethal dose: 120 mg/kg	N/R	FDWU** -,-,1931
subcutaneous dog	lowest published lethal dose: 120 mg/kg	N/R	FDWU** -,-,1931
subcutaneous frog	lowest published lethal dose: 140 mg/kg	N/R	HBAMAK 4,1289,1935
subcutaneous mouse	lethal dose (50 percent kill): 170 mg/kg	N/R	AEPPAE 227,129,1955
subcutaneous pigeon	lowest published lethal dose: 150 mg/kg	N/R	FDWU** -,-,1931
subcutaneous rat	lethal dose (50 percent kill): 151 mg/kg	N/R	ARZNAD 20,1338,1970
subcutaneous rabbit	lowest published lethal dose: 250 mg/kg	N/R	HBAMAK 4,1289,1935

OTHER MULTIPLE DOSE DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
N/R	N/R	N/R	N/R

REVIEWS:
ORGANIZATION	STANDARD	REFERENCE
TOXICOLOGY REVIEW		DIMON* 39,678,1993

STANDARDS AND REGULATIONS:
ORGANIZATION	STANDARD	REFERENCE
N/R	N/R	N/R

NIOSH DOCUMENTATION AND SURVEILLANCE:
ORGANIZATION	STANDARD or SURVEY	REFERENCE
National Occupational Exposure Survey 1983	National Occupational Exposure Survey 1983: Hazard Code: X4373; Number of Industries 1; Total Number of Facilities 17; Number of Occupations 2; Total Number of Employees Exposed 563; Total Number of Female Employees Exposed 481

REFERENCES:
CODEN	REFERENCE
AEPPAE	Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC.
AIPTAK	Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898-
AITEAT	Archivum Immunologiae et Therapiae Experimentalis. (Ars Polona, POB 1001, 00-068 Warsaw 1, Poland) V.10- 1962-
AJEMEN	American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983-
ARZNAD	Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
DIMON*	Disease-a Month (Chicago : Year Book Publishers) V. 24- 1978-
EJCPAS	European Journal of Clinical Pharmacology. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.3- 1970-
FATOAO	Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939-
FDWU**	"Ueber die Wirkung Verschiedener Gifte Auf Vogel, Dissertation," Forchheimer, L., Pharmakologischen Institut der Universitat Wurzburg, Fed. Rep. Ger., 1931
HBAMAK	"Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.)
JCPCDT	Journal of Cardiovascular Pharmacology. (Raven Press, 1140 Ave. of the Americas, New York, NY 10036) V.1- 1979-
JIDEAE	Journal of Investigative Dermatology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1938-
JMCMAR	Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963-
JPETAB	Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
THERAP	Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946-
USXXAM	United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231)