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25614-03-3

25614-03-3 structure
25614-03-3 structure
  • Name: Bromocriptine
  • Chemical Name: bromocriptine
  • CAS Number: 25614-03-3
  • Molecular Formula: C32H40BrN5O5
  • Molecular Weight: 654.59400
  • Catalog: API Nervous system medication Anti-shock palsy
  • Create Date: 2018-07-04 23:21:40
  • Modify Date: 2024-01-07 08:57:26
  • Bromocriptine is a potent dopamine D2/D3 receptor agonist, which binds D2 dopamine receptor with pKi of 8.05±0.2.

Name bromocriptine
Synonyms Bromocryptine
MFCD00870213
Bromoergocryptine
Bromergocryptine
Bromoergocriptine
Bromocriptinum
Ergoset
EINECS 247-128-5
Bromocriptin
Description Bromocriptine is a potent dopamine D2/D3 receptor agonist, which binds D2 dopamine receptor with pKi of 8.05±0.2.
Related Catalog
Target

pKi: 8.05±0.2 (dopamine D2 receptor)[1]

In Vitro Bromocriptine stimulates [35S]-GTPγS binding at D2 dopamine receptor expressed in CHO cells with pEC50 of 8.15±0.05[1]. Bromocriptine also is a strong inhibitor of brain nitric oxide synthase. The ergot alkaloid Bromocriptine (BKT) is found to act as a strong inhibitor of purified neuronal nitric oxide synthase (NOS) (IC50=10±2 μM) whereas it is poorly active towards inducible macrophage NOS (IC50>100 μM) [2]. Bromocriptine is found to inhibit the activity of at least one human cytochrome P450 enzyme. Bromocriptine is a potent inhibitor of CYP3A4 with a calculated IC50 value for the interaction of 1.69 μM[3].
In Vivo Bromocriptine (a dopamine agonist) treatment (2 mg/kg, i.p.) group shows significant anti-immobility action as compared to control. When Bromocriptine administered 30 min after the last dose of 7 days MPE treatment and subjected to FST, this dopaminergic agonist produces significant and dose dependent potentiation of anti-immobility action of MPE (200 mg/kg, p.o.) as compared to MPE treatment alone. Bromocriptine (a dopamine agonist) treatment (2 mg/kg, i.p.) group shows a significant reduction of immobility time as compared to control. Bromocriptine administration after 7 days pretreatment with MPE (100 and 200 mg/kg, p.o.) shows significant and dose dependent potentiation of anti-immobility action of MPE as compared to MPE treatment alone[4]. Intraperitoneal administration of Bromocriptine induces a significant, dose dependent (0.1 mg and 1 mg/Kg) decrease in pain scores in CCI-IoN group when compared to sham and its effect lasted for 6 h. The highest dose induces the highest score decrease, (P<0.01). As a positive control SKF8129 (DR1 agonist) is used. Its intraperitoneal administration induces a non-significant increase in the SMA score when compared to sham (saline-injected). Intracisternal administration of Bromocriptine decreases significantly the SMA score when compared to sham (saline-injected). Bromocriptine effect lasted for 20 min. Intraperitoneal administration of Bromocriptine induces a significant dose dependent decrease in SMA score in CCI-IoN?+?6-OHDA lesioned group compared to that of sham. Its effect lasted for 6 h. SKF81297 administration increases the allodynic score. Intracisternal administration of Bromocriptine decreases significantly the SMA score compared to that of sham (saline-injected rats) and its effect lasted for 30 min[5].
Kinase Assay The [35S]-GTPγS binding assay is carried out. Cell membranes (25 ±75 ug) are incubated in Buffer B containing 0.1 mM dithiothreitol (DTT) and 1 uM GDP and drugs in a volumeof 0.9 mL for 30 min at 30°C. This preincubation ensures that the agonists tested are at equilibrium when the [35S]-GTPγS (50±150 pM, final concentration) is added (in 100 uL ofBuffer B) to initiate the reaction. The assay mixture is incubated for a further 20 min unless otherwise stated. The assays are terminated by rapid filtration and bound radio-activity determined as described for the radio-ligand binding assays above. The total binding of [35S]-GTPγS is less than 20% of that added[1].
Animal Admin Mice[4] Swiss mice (20-25 g) of either sex (total 150) are used. Bromocriptine mesylate is used as dopamine receptor (D2) agonist. Haloperidol is diluted in distilled water which is used for a vehicle of injection. Bromocriptine mesylate is dissolved in one drop of glacial acetic acid and made up to volume in distilled water. Imipramine is dissolved in 0.9% normal saline. Haloperidol (0.1 mg/kg, i.p.) and Bromocriptine mesylate (2 mg/kg, i.p.) are administered for 7 days in groups of mice in Forced Swimming Test (FST) and Tail Suspension Test (TST). Imipramine (10 mg/kg, p.o.) as a standard is administered in positive control groups for 7 days. Rats[5] Adult male Sprague-Dawley rats (N=112, 275-325 g) are used. Two weeks after the 6-OHDA injection, the animals are briefly (<3 min) anesthetized with 2 % halothane using a mask and received for intracisternal administration Bromocriptine (7 μg/kg dissolved in 5 μL vehicle) or the vehicle alone (5 μL of 0.9 % saline). For i.p. injection we used Bromocriptine (1 mg/kg) and SKF81297 (3 mg/kg dissolved in 0.9 % saline) concentrations. Following a recovery period (<2 min), the rats are placed in the observation field for 40 min period-test by a blind-experimenter.
References

[1]. Gardner B, et al. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.

[2]. Renodon A, et al. Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.FEBS Lett. 1997 Apr 7;406(1-2):33-6.

[3]. Wynalda MA, et al. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4.

[4]. Rana DG, et al. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014 Jan;35(1):90-7.

[5]. Dieb W, et al. Nigrostriatal dopaminergic depletion increases static orofacial allodynia. J Headache Pain. 2016;17:11.

Density 1.52 g/cm3
Boiling Point 891.3ºC at 760 mmHg
Molecular Formula C32H40BrN5O5
Molecular Weight 654.59400
Flash Point 492.8ºC
Exact Mass 653.22100
PSA 118.21000
LogP 3.39740
Vapour Pressure 4.15E-34mmHg at 25°C
Index of Refraction 1.696

CHEMICAL IDENTIFICATION

RTECS NUMBER :
KE7625000
CHEMICAL NAME :
Ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpr opyl)-, (5'-alpha)-
CAS REGISTRY NUMBER :
25614-03-3
LAST UPDATED :
199703
DATA ITEMS CITED :
38
MOLECULAR FORMULA :
C32-H40-Br-N5-O5
MOLECULAR WEIGHT :
654.68

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
6 mg/kg/60D-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
72 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 :
>800 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 :
Unreported
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
200 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 - rabbit
DOSE/DURATION :
>1 gm/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 - rabbit
DOSE/DURATION :
12 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
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
7 gm/kg/2Y-C
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
2423 ug/kg
SEX/DURATION :
lactating female 3 week(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - other effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1500 ug/kg
SEX/DURATION :
lactating female 9 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1500 ug/kg
SEX/DURATION :
lactating female 15 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1750 ug/kg
SEX/DURATION :
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
21700 ug/kg
SEX/DURATION :
female 28 week(s) pre-mating female 1-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - respiratory system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
3500 ug/kg
SEX/DURATION :
female 14 day(s) pre-mating female 1-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
11900 ug/kg
SEX/DURATION :
female 77 day(s) pre-mating female 1-42 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
11200 ug/kg
SEX/DURATION :
female 44 day(s) pre-mating female 1-12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
2800 ug/kg
SEX/DURATION :
female 24-52 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - body wall
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
70 mg/kg
SEX/DURATION :
female 13-19 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - behavioral
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
1950 ug/kg
SEX/DURATION :
female 5-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
5100 ug/kg
SEX/DURATION :
lactating female 3 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - postpartum
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
17500 ug/kg
SEX/DURATION :
male 35 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
88 mg/kg
SEX/DURATION :
female 1-22 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) Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
8125 ug/kg
SEX/DURATION :
female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
84 mg/kg
SEX/DURATION :
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
200 mg/kg
SEX/DURATION :
female 50 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
212 mg/kg
SEX/DURATION :
female 32 day(s) pre-mating female 21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
4 mg/kg
SEX/DURATION :
male 10 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
750 ug/kg
SEX/DURATION :
female 43-48 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - abortion
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
600 ug/kg
SEX/DURATION :
female 42-47 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - abortion
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
8 mg/kg
SEX/DURATION :
female 27-30 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - other effects to embryo
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
400 ug/kg
SEX/DURATION :
male 50 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
3 mg/kg
SEX/DURATION :
male 84 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
75200 ug/kg
SEX/DURATION :
female 42-49 week(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition Reproductive - Maternal Effects - postpartum
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
22400 ug/kg
SEX/DURATION :
female 42-44 week(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - other effects Endocrine - estrogenic
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
1 mg/kg
SEX/DURATION :
female 23 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

MUTATION DATA

TEST SYSTEM :
Rodent - rat
DOSE/DURATION :
4 mg/kg
REFERENCE :
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 36,2223,1976 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6252 No. of Facilities: 9 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 339 (estimated) No. of Female Employees: 170 (estimated)

~91%

25614-03-3 structure

25614-03-3

Literature: Megyeri, Gabor; Keve, Tibor Synthetic Communications, 1989 , vol. 19, # 20 p. 3415 - 3430

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25614-03-3 structure

25614-03-3

Literature: US4816587 A1, ;
Precursor  2

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