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Bromocriptine (INN; trade names Parlodel, Cycloset, Brotin (Pakistan)), an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease (PD), hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.

Indications

Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly may all be caused by pituitary problems, such as hyperprolactinaemia, and therefore, these problems may be treated with this drug. Bromocriptine has completely treated gestational macromastia eliminating the need for reduction surgery, in a recent case.^[1] It has also been used in treating nonpuerperal mastitis.^[2] Since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal.^[3]^[4] In 2009, bromocriptine mesylate was approved by the FDA for treatment of type 2 diabetes under the trade name Cycloset (VeroScience). It is currently unknown how this drug improves glycemic control, but it has been shown to reduce HbA1c by ~0.5 percentage points.^[5]

Pharmacology

Bromocriptine is a potent agonist at dopamine D2 receptors^[6] and various serotonin receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.^[7]

Bromocriptine agonizes the following monoamine receptors:^[8]

Dopamine D₁ family
- D₁ (K_i=682 nM)
- D₅ (K_i=496 nM)
Dopamine D₂ family
- D₂ (K_i=2.96 nM)
- D₃ (K_i=5.42 nM)
- D₄ (K_i=328 nM)
Serotonin 5-HT
- 5-HT_1A (K_i=12.9 nM)
- 5-HT_1B (K_i=355 nM)
- 5-HT_1D (K_i=10.7 nM)
- 5-HT_2A (K_i=107 nM)
- 5-HT_2B (K_i=56.2 nM)
- 5-HT_2C (K_i=741 nM)
- 5-HT₆ (K_i=33 nM)
Adrenergic α family
- α_1A (K_i=4.17 nM)
- α_1B (K_i=1.38 nM)
- α_1D (K_i=1.12 nM)
- α_2A (K_i=11.0 nM)
- α_2B (K_i=34.7 nM)
- α_2C (K_i=28.2 nM)
Adrenergic β family
- β₁ (K_i=589 nM)
- β₂ (K_i=741 nM)

Side effects

Most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre.^[9] Vasospasms with serious consequences such as myocardial infarction and stroke that have been reported in connection with the puerperium, appear to be extremely rare events.^[10] Peripheral vasospasm (of the fingers or toes) can cause Raynaud's Phenomenon. Bromocriptine use has been anecdotally associated with causing or worsening psychotic symptoms (its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine).^[11] Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.^[12]

Use to suppress milk production after childbirth was reviewed in 2014 and it was concluded that in this context a causal association with serious cardiovascular, neurological or psychiatric events could not be excluded with an overall incidence rate estimated to range between 0.005% and 0.04%. Additional safety precautions and stricter prescribing rules were suggested based on the data.^[13]^[14]

Chemistry

Like all ergopeptides, bromocriptine is a cyclol; two peptide groups of its tripeptide moiety are crosslinked, forming the >N-C(OH)< juncture between the two rings with the amide functionality.

Bromocriptine is a semisynthetic derivative of a natural ergot alkaloid, ergocryptine (a derivative of lysergic acid), which is synthesized by bromination of ergocryptine using N-bromosuccinimide.^[15]^[16]

References

^ Ezem, Osuagwu, Opara (February 2011). "Gestational gigantomastia with complete resolution in a Nigerian woman". BMJ. 2011. doi:10.1136/bcr.01.2010.2632. PMC 3062818. PMID 22707463.
^ Goepel E, Pahnke VG (1991). "Successful therapy of nonpuerperal mastitis – already routine or still a rarity?". Geburtshilfe Frauenheilkd (in German). 51 (2): 109–16. doi:10.1055/s-2007-1023685. PMID 2040409.
^ AJ Giannini, P Baumgartel, LR DiMarzio. Bromocriptine therapy in cocaine withdrawal. J. Clinical Pharmacology. 27: 267-270,1987.
^ FS Tenant, AA Sagherian. Double-blind comparison of amantadine hydrochloride and bromocriptine mesylate for ambulatory withdrawal from cocaine dependence. Archives of General Medicine. 147: 109-112,1987.
^ Pijl H, Ohashi S, Matsuda M, et al. (August 2000). "Bromocriptine: a novel approach to the treatment of type 2 diabetes". Diabetes Care. 23 (8): 1154–61. doi:10.2337/diacare.23.8.1154. PMID 10937514.
^ De Leeuw Van Weenen, J. E.; Parlevliet, E. T.; Maechler, P.; Havekes, L. M.; Romijn, J. A.; Ouwens, D. M.; Pijl, H.; Guigas, B. (2010). "The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the α2-adrenergic receptors in beta cells". Biochemical Pharmacology. 79 (12): 1827–36. doi:10.1016/j.bcp.2010.01.029. PMID 20138024.
^ Shirasaki, Y; Sugimura, M; Sato, T (September 2010). "Bromocriptine, an ergot alkaloid, inhibits excitatory amino acid release mediated by glutamate transporter reversal.". European Journal of Pharmacology. 643 (1): 48–57. doi:10.1016/j.ejphar.2010.06.007. PMID 20599932.
^ National Institute ofMental Health. PDSD Ki Database (Internet) [cited 2013 Jul 24]. ChapelHill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
^ Weil, C. (1986). "The safety of bromocriptine in long-term use: a review of the literature". Current medical research and opinion. 10 (1): 25–51. doi:10.1185/03007998609111089. PMID 3516579.
^ Iffy, L; McArdle, JJ; Ganesh, V; Hopp, L (1996). "Bromocriptine related atypical vascular accidents postpartum identified through medicolegal reviews". Medicine and law. 15 (1): 127–34. PMID 8691994.
^ Boyd, A. (1995). "Bromocriptine and psychosis: a literature review". The Psychiatric quarterly. 66 (1): 87–95. doi:10.1007/BF02238717. PMID 7701022.
^ Todman, D.; Oliver, W.; Edwards, R. (1990). "Pleuropulmonary fibrosis due to bromocriptine treatment for Parkinson's disease". Clinical and experimental neurology. 27: 79–82. PMID 2129961.
^ EMA Statement "CMDh endorses restricted use of bromocriptine for stopping breast milk production"
^ http://m.aerzteblatt.de/news/59857.htm "EMA rät vom Abstillmittel Bromocriptin ab", article in Ärzteblatt
^ E. Fluckiger, A. Hofmann, U.S. Patent 3,752,814 (1973)
^ A. Hofmann, E. Flueckiger, DE 1926045 (1969)

External links

www.AcromegalyCommunity.com: Emotional and communal support for those touched by Acromegaly- page discussing drug, side effects, and prescription programs
MedlinePlus DrugInfo medmaster-a682079
http://www.drugs.com/pro/bromocriptine.html

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 周産期心筋症：治療および予後 peripartum cardiomyopathy treatment and prognosis
2. 高プロラクチン血症のマネージメント management of hyperprolactinemia
3. 2型糖尿病における持続性高血糖のマネージメント management of persistent hyperglycemia in type 2 diabetes mellitus
4. パーキンソン病に対する神経保護療法 neuroprotective therapy for parkinson disease
5. 妊娠中の乳腺刺激腺腫（プロラクチン産生腫瘍）のマネージメント management of lactotroph adenoma prolactinoma during pregnancy

English Journal

Inhibition of prolactin with bromocriptine for 28days increases blood-brain barrier permeability in the rat.

Rosas-Hernandez H1, Ramirez M1, Ramirez-Lee MA1, Ali SF2, Gonzalez C3.
Neuroscience.Neuroscience.2015 Jun 3. pii: S0306-4522(15)00517-5. doi: 10.1016/j.neuroscience.2015.05.066. [Epub ahead of print]
The blood-brain barrier (BBB) is necessary for the proper function of the brain. Its maintenance is regulated by endogenous factors. Recent evidences suggest prolactin (PRL) regulates the BBB properties in vitro, nevertheless no evidence of its effects have been reported in vivo. The aim of this stu
PMID 26047726

Maternal prolactin inhibition causes changes in leptin at 22- and 30-day-old pups.

Carvalho JC1, de Oliveira E1, Peixoto-Silva N1, Fraga MC1, Nobre JL1, Lisboa PC1, Moura EG1.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme.Horm Metab Res.2015 Jun;47(7):528-36. doi: 10.1055/s-0034-1394379. Epub 2014 Nov 5.
Breastfeeding is associated with obesity prevention. We showed previously that prolactin inhibition at the end of lactation causes hyperleptinemia at weaning (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin resistance (PN180). Here, we evaluate the source of neonatal hyp
PMID 25372778

Rationale and design of a randomized, controlled multicentre clinical trial to evaluate the effect of bromocriptine on left ventricular function in women with peripartum cardiomyopathy.

Haghikia A1, Podewski E, Berliner D, Sonnenschein K, Fischer D, Angermann CE, Böhm M, Röntgen P, Bauersachs J, Hilfiker-Kleiner D.
Clinical research in cardiology : official journal of the German Cardiac Society.Clin Res Cardiol.2015 May 31. [Epub ahead of print]
BACKGROUND: Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essen
PMID 26026286

Japanese Journal

Transdermal Administration of Bromocriptine

DEGIM Ismail Tuncer,ACARTURK Fusun,ERDOGAN Deniz,DEMIREZ LORTLAR Nese
Biological & pharmaceutical bulletin 26(4), 501-505, 2003-04-01
… Commercial BRC tablets (Parlodel^R) were also given to rabbits orally and plasma levels were compared. …
NAID 110003608461

乳汁分泌の内分泌性調節

青野敏博
日本産科婦人科學會雜誌 42(8), 867-872, 1990-08-01
… On the other hand, Parlodel-MR and terguride effectively, suppressed lactation in the puerperial period, and had less side effects compared to bromocriptine. …
NAID 110002168040

Related Pictures

Buy Bromocriptine (Parlodel) - Optimal brand names parlodel why is parlodel Parlodel tabletki – Encyklopedia leków PARLODEL 2 5MG 14 COMP Parlodel prescription drug /side effects PARLODEL SRO Yavaş Salımlı Kapsül 2.5 Drugs reference index « Parlodel » PARLODEL Tablet 2.5 mg 30 tabletlik

★リンクテーブル★

リンク元	「ブロモクリプチン」

「ブロモクリプチン」

Bromocriptine
Systematic (IUPAC) name
	(5′α)-2-Bromo-12′-hydroxy-5′-(2-methylpropyl)-3′,6′,18-trioxo-2′-(propan-2-yl)ergotaman
Clinical data
Trade names	Parlodel, Brotin
AHFS/Drugs.com	Monograph,International Drug Names
MedlinePlus	a682079
Pregnancy; category	AU: A; US: B (No risk in non-human studies); ;
Routes of; administration	oral, intravenous
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	28% of oral dose absorbed
Metabolism	Extensively liver-mediated
Biological half-life	12-14 hours
Excretion	85% bile (faeces), 2.5-5.5% urine
Identifiers
CAS Number	25614-03-3
ATC code	G02CB01 (WHO) N04BC01 (WHO)
PubChem	CID 31101
IUPHAR/BPS	35
DrugBank	DB01200
ChemSpider	28858
UNII	3A64E3G5ZO
KEGG	D03165
ChEBI	CHEBI:3181
ChEMBL	CHEMBL493
Synonyms	2-Bromoergocriptine
Chemical data
Formula	C32H40BrN5O5
Molar mass	654.595 g/mol
	SMILES BrC1=C(C[C@H]2N(C)C3)C4=C(C=CC=C4C2=C[C@H]3C(N[C@]5(C(C)C)O[C@@]6(N([C@@H](CC(C)C)C(N7CCC[C@H]76)=O)C5=O)O)=O)N1 ;
	InChI InChI=1S/C32H40BrN5O5/c1-16(2)12-24-29(40)37-11-7-10-25(37)32(42)38(24)30(41)31(43-32,17(3)4)35-28(39)18-13-20-19-8-6-9-22-26(19)21(27(33)34-22)14-23(20)36(5)15-18/h6,8-9,13,16-18,23-25,34,42H,7,10-12,14-15H2,1-5H3,(H,35,39)/t18-,23-,24+,25+,31-,32+/m1/s1 ; Key:OZVBMTJYIDMWIL-AYFBDAFISA-N ;
(verify)

　　[★]

英: bromocriptine
化: メシル酸ブロモクリプチン bromocriptine mesilate
商: パーロデル Parlodel、パルキゾン、アップノールB、エレナント、コーパデル、デパロ、パーロミン、パドパリン、パロラクチン、メーレーン
関

パーキンソン病治療薬

ドパミン受容体作動薬

特徴

(麦角)バッカクアルカロイドの誘導体。

構造

作用機序

薬理作用

プロラクチンや成長ホルモンに対する生理的抑制因子

動態

適応

1. 産褥性乳汁分泌抑制、乳汁漏出症
2. 高プロラクチン血性排卵障害
3. 高プロラクチン血性下垂体腺腫(外科的処置を必要としない場合に限る)
4. 末端肥大症、下垂体性巨人症
5. パーキンソン症候群

注意

禁忌

副作用

添付文書

[gestational-1] Ezem, Osuagwu, Opara (February 2011). "Gestational gigantomastia with complete resolution in a Nigerian woman". BMJ. 2011. doi:10.1136/bcr.01.2010.2632. PMC 3062818. PMID 22707463.

[Goepel-2] Goepel E, Pahnke VG (1991). "Successful therapy of nonpuerperal mastitis – already routine or still a rarity?". Geburtshilfe Frauenheilkd (in German). 51 (2): 109–16. doi:10.1055/s-2007-1023685. PMID 2040409.

[3] AJ Giannini, P Baumgartel, LR DiMarzio. Bromocriptine therapy in cocaine withdrawal. J. Clinical Pharmacology. 27: 267-270,1987.

[4] FS Tenant, AA Sagherian. Double-blind comparison of amantadine hydrochloride and bromocriptine mesylate for ambulatory withdrawal from cocaine dependence. Archives of General Medicine. 147: 109-112,1987.

[5] Pijl H, Ohashi S, Matsuda M, et al. (August 2000). "Bromocriptine: a novel approach to the treatment of type 2 diabetes". Diabetes Care. 23 (8): 1154–61. doi:10.2337/diacare.23.8.1154. PMID 10937514.

[6] De Leeuw Van Weenen, J. E.; Parlevliet, E. T.; Maechler, P.; Havekes, L. M.; Romijn, J. A.; Ouwens, D. M.; Pijl, H.; Guigas, B. (2010). "The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the α2-adrenergic receptors in beta cells". Biochemical Pharmacology. 79 (12): 1827–36. doi:10.1016/j.bcp.2010.01.029. PMID 20138024.

[7] Shirasaki, Y; Sugimura, M; Sato, T (September 2010). "Bromocriptine, an ergot alkaloid, inhibits excitatory amino acid release mediated by glutamate transporter reversal.". European Journal of Pharmacology. 643 (1): 48–57. doi:10.1016/j.ejphar.2010.06.007. PMID 20599932.

[8] National Institute ofMental Health. PDSD Ki Database (Internet) [cited 2013 Jul 24]. ChapelHill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php

[9] Weil, C. (1986). "The safety of bromocriptine in long-term use: a review of the literature". Current medical research and opinion. 10 (1): 25–51. doi:10.1185/03007998609111089. PMID 3516579.

[10] Iffy, L; McArdle, JJ; Ganesh, V; Hopp, L (1996). "Bromocriptine related atypical vascular accidents postpartum identified through medicolegal reviews". Medicine and law. 15 (1): 127–34. PMID 8691994.

[11] Boyd, A. (1995). "Bromocriptine and psychosis: a literature review". The Psychiatric quarterly. 66 (1): 87–95. doi:10.1007/BF02238717. PMID 7701022.

[12] Todman, D.; Oliver, W.; Edwards, R. (1990). "Pleuropulmonary fibrosis due to bromocriptine treatment for Parkinson's disease". Clinical and experimental neurology. 27: 79–82. PMID 2129961.

[13] EMA Statement "CMDh endorses restricted use of bromocriptine for stopping breast milk production"

[14] ttp://m.aerzteblatt.de/news/59857.htm "EMA rät vom Abstillmittel Bromocriptin ab", article in Ärzteblatt

[15] E. Fluckiger, A. Hofmann, U.S. Patent 3,752,814 (1973)

[16] A. Hofmann, E. Flueckiger, DE 1926045 (1969)

v t e Tocolytics/labor repressants (G02CA)

β₂ adrenoreceptor agonists	Buphenine Fenoterol Hexoprenaline Ritodrine Terbutaline

Oxytocin antagonists	Atosiban

NSAIDs	Indometacin

Calcium channel blockers	Nifedipine

Myosin inhibitors	Magnesium sulfate

v t e Ergolines

Lysergic acid derivatives	2-Bromo-LSD (BOL-148) Bromocriptine Cabergoline Dihydroergocornine Dihydroergocristine Dihydroergocryptine Dihydroergometrine (Dihydroergonovine, Dihydroergobasine) Dihydroergosine Dihydroergotamine Epicriptine Ergine (LSA; LA-111; Lysergamide) Ergocornine Ergocristine Ergocryptine Ergoloid (Dihydroergotoxine) Ergometrine (Ergonovine, Ergobasine) Ergometrinine Ergotamine Ergotoxine Ergovaline Lisuride LSD LSH Lysergic Acid Lysergic acid cyclobutylamide Lysergic acid cyclopentylamide Lysergic Acid Methyl Ester Lysergol Mesulergine Metergoline Methergine (Methylergometrine, Methylergonovine, Methylergobasine) Methysergide Pergolide Syntometrine

Psychedelic lysergamides	1P-ETH-LAD 1P-LSD AL-LAD ALD-52 BU-LAD CYP-LAD DAL DAM-57 Ergonovine ETH-LAD IP-LAD LAE-32 LSD LPD-824 LSM-775 LSH LSD-Pip Lysergic Acid 2-Butylamide Lysergic Acid 2,4-Dimethylazetidide Lysergic Acid 3-Pentylamide Methylergonovine Methylisopropyllysergamide MLD-41 PARGY-LAD PRO-LAD

Other ergolines	Ergoline

Natural sources	Achnatherum robustum (Sleepy Grass) Claviceps spp. (Ergot) Morning glory: Argyreia nervosa (Hawaiian Baby Woodrose), Ipomoea spp.(Morning Glory, Tlitliltzin, Badoh Negro), Rivea corymbosa (Coaxihuitl, Ololiúqui)

匿名

検索

案内

案内

Parlodel