*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : YS9325000
CHEMICAL NAME : Urea,
3-(9,10-didehydro-6-methylergolin-8-alpha-yl)-1,1-die
thyl-, maleate (1:1)
CAS REGISTRY NUMBER : 19875-60-6
LAST UPDATED : 199212
DATA ITEMS CITED : 29
MOLECULAR FORMULA : C20-H26-N4-O.C4-H4-O4
MOLECULAR WEIGHT : 454.58
WISWESSER LINE NOTATION : T C6656 1A P GN LM CUTT&&J EMVN2&2 G1 &QV1U1VQ
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Cuvalit
* 3-(9,10-Didehydro-6-methylergolin-8-yl)-1,1-diethylurea hydrogen maleate
* 3-(9,10-Didehydro-6-methylergolin-8-alpha-yl)-1,1-diethylurea maleate
(1:1)
* Lisuride hydrogen maleate
* Lisuride maleate
* Lysenyl
* Lysenyl bimaleate
* Lysenyl hydrogen maleate
* 1-((5R,8S)-6-Methyl-9,10-didehydro-8-ergolinyl)-3,3-diethylurea hydrogen
maleate
* Urea, N'-((8-alpha)-9,10-didehydro-6-methylergolin-8-yl)-N,N-diethyl-,
(Z)-2-butenedioate
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 714 ng/kg
TOXIC EFFECTS :
Behavioral - headache
Gastrointestinal - nausea or vomiting
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 16,220,1966
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Human - man
DOSE/DURATION : 1429 ng/kg/3M-C
TOXIC EFFECTS :
Cardiac - other changes
Gastrointestinal - nausea or vomiting
Skin and Appendages - sweating
REFERENCE :
CHETBF Chest. (American College of Chest Physicians, 911 Busse Hwy, Park
Ridge, IL 60068) V.57- 1970- Volume(issue)/page/year: 91,792,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 138 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 12200 ug/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2900 ug/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 405 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 530 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 14800 ug/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 123 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - excitement
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1165,1981
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 350 mg/kg/35D-C
TOXIC EFFECTS :
Liver - changes in liver weight
Endocrine - adrenal cortex hyperplasia
Endocrine - changes in thymus weight
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1177,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 151 mg/kg/54W-C
TOXIC EFFECTS :
Endocrine - other changes
Endocrine - changes in adrenal weight
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 13,716,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 3 gm/kg/30D-C
TOXIC EFFECTS :
Endocrine - adrenal cortex hyperplasia
Blood - changes in spleen
Biochemical - Metabolism (Intermediary) - Plasma proteins not involving
coagulation
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1177,1981
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 42 ug/kg
SEX/DURATION : lactating female 7 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
Reproductive - Maternal Effects - other effects
REFERENCE :
BJOGAS British Journal of Obstetrics and Gynaecology. (Blackwell Scientific
Pub. Ltd., POB 88, Oxford, UK) V.82- 1975- Volume(issue)/page/year:
86,905,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 168 ug/kg
SEX/DURATION : lactating female 14 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
Reproductive - Maternal Effects - other effects
REFERENCE :
GOBIDS Gynecologic and Obstetric Investigation. (S. Karger Pub., Inc., 79
Fifth Ave., New York, NY 10003) V.9- 1978- Volume(issue)/page/year:
10,95,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 242 ug/kg
SEX/DURATION : lactating female 4 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
REFERENCE :
CCCCAK Collection of Czechoslovak Chemical Communications. (Academic Press
Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1929-
Volume(issue)/page/year: 49,2828,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 350 mg/kg
SEX/DURATION : male 35 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland,
accessory glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1177,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1750 mg/kg
SEX/DURATION : female 35 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,1177,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 80 ug/kg
SEX/DURATION : female 5 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
REFERENCE :
CCCCAK Collection of Czechoslovak Chemical Communications. (Academic Press
Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1929-
Volume(issue)/page/year: 49,2828,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 50 ug/kg
SEX/DURATION : lactating female 5 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
REFERENCE :
ENEXAM Endocrinologia Experimentalis. (Karger-Libri, P.O. Box, CH-4009
Basel, Switzerland) V.1- 1964- Volume(issue)/page/year: 8,51,1974
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 600 ug/kg
SEX/DURATION : female 6 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - breasts, lactation (prior to or during
pregnancy)
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,2593,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 70 mg/kg
SEX/DURATION : male 35 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,2593,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 35 mg/kg
SEX/DURATION : female 35 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - ovaries, fallopian tubes
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,2593,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 18 mg/kg
SEX/DURATION : male 60 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland,
accessory glands
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2299,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 75 mg/kg
SEX/DURATION : female 15-18 day(s) after conception
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - eye/ear
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2346,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 30 mg/kg
SEX/DURATION : female 6-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2311,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 75 mg/kg
SEX/DURATION : multigenerations
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2346,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 7500 ug/kg
SEX/DURATION : multigenerations
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2346,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 130 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2338,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 1300 ug/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 15,2338,1981
*** END OF RECORD ***