CB-154 mesylate

Bromocriptine mesylate is a potent dopamine D2/D3 receptor agonist, which binds D2 dopamine receptor with pKi of 8.05±0.2.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Natural Products >> Others

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

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].

Bromocriptine mesylate (2 mg/kg, i.p.) is administered for 7 days in groups of mice in forced swimming test (FST) and tail suspension test (TST). Bromocriptine 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 treatment 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]. Intracisternal administration of Bromocriptine decreases significantly the static mechanical allodynia (SMA) score compared to that of sham (saline-injected rats) and its effect lasted for 30 min. 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). Bromocriptine effect lasts 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 lasts for 6 h[5].

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 volume of 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].

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.

[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.

SCH 23390 hydrochloride | Levodopa | Cabergoline | Thioridazine hydrochloride | Brexpiprazole | Domperidone | Trifluoperazine dihydrochloride | pimozide | Risperidone | SKF38393 HCl | Cariprazine | SERTINDOLE | Fluphenazine (dihydrochloride) | Nomifensine | Ropinirole hydrochloride

MOLECULAR FORMULA :

C32-H4O-Br-N5-O5.C-H4-O3-S

MOLECULAR WEIGHT :

714.43

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

50 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified

REFERENCE :

LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 340,1410,1992

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

650 ug/kg/9D-I

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - headache Cardiac - cardiomyopathy including infarction

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 118,199,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

375 ug/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 105,838,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1 mg/kg/20D-I

TOXIC EFFECTS :

Behavioral - toxic psychosis

REFERENCE :

AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 143,935,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

52 mg/kg/35W-I

TOXIC EFFECTS :

Brain and Coverings - changes in cerebral spinal fluid

REFERENCE :

NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 35,1193,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,809,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,809,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

10500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 29,1231,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2502 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,809,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

189 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,809,1979

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

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,809,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

8200 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

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: 10,232,1979 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1400 mg/kg

SEX/DURATION :

lactating female 1-14 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum

REFERENCE :

JRPMAP Journal of Reproductive Medicine. (2 Jacklynn Ct., St. Louis, MO 63132) V.3- 1969- Volume(issue)/page/year: 33,630,1988

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

42 mg/kg

SEX/DURATION :

female 1-7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- Volume(issue)/page/year: 30,1358,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

60 mg/kg

SEX/DURATION :

female 6 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Maternal Effects - other effects

REFERENCE :

BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year: 34,788,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

3 mg/kg

SEX/DURATION :

male 15 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

REFERENCE :

IJANDP International Journal of Andrology. (Scriptor Publisher ApS, 15 Gasvaerksvej, DK-1656 Copenhagen V, Denmark) V.1- 1978- Volume(issue)/page/year: 5,331,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

10500 ug/kg

SEX/DURATION :

female 1-7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- Volume(issue)/page/year: 30,1358,1974

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

225 ug/kg

SEX/DURATION :

female 3 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- Volume(issue)/page/year: 24,1130,1968

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

10500 ug/kg

SEX/DURATION :

female 6-8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum

REFERENCE :

EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- Volume(issue)/page/year: 24,1130,1968

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2 mg/kg

SEX/DURATION :

female 5 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - abortion

REFERENCE :

TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 50,189,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

35 mg/kg

SEX/DURATION :

female 14-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo

REFERENCE :

GCENA5 General and Comparative Endocrinology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1961- Volume(issue)/page/year: 39,118,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

20 mg/kg

SEX/DURATION :

male 10 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

REFERENCE :

IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 23,679,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3 mg/kg

SEX/DURATION :

lactating female 3 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,51,1976 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4920 No. of Facilities: 27 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 499 (estimated) No. of Female Employees: 225 (estimated)