bromocriptine bromocriptine bromocriptine, originally marketed as parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes. bromocriptineclinical datatrade namesoriginally parlodel, subsequently manyother names2-bromoergocriptine; cb-154ahfs/drugs.commonograph, international drug namesmedlineplusa682079pregnancycategory au: a routes ofadministrationby mouth, vaginal, intravenousatc codeg02cb01 (who) n04bc01 (who)legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability28% of oral dose absorbedmetabolismextensively liver-mediatedelimination half-life12–14 hoursexcretion85% bile (feces), 2.5–5.5% urineidentifiers iupac name (5′α)-2-bromo-12′-hydroxy-5′-(2-methylpropyl)-3′,6′,18-trioxo-2′-(propan-2-yl)ergotaman cas number25614-03-3 ypubchem cid31101iuphar/bps35drugbankdb01200 ychemspider28858 yunii3a64e3g5zokeggd03165 ychebichebi:3181 ychemblchembl493 ycomptox dashboard (epa)dtxsid1022687 echa infocard100.042.829 chemical and physical dataformulac32h40brn5o5molar mass654.606 g·mol−13d model (jsmol)interactive image smiles brc1=c(c2n(c)c3)c4=c(c=cc=c4c2=c3c(n5(c(c)c)o6(n((cc(c)c)c(n7ccc76)=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 ykey:ozvbmtjyidmwil-ayfbdafisa-n y (verify) it was patented in 1968 and approved for medical use in 1975. medical uses bromocriptine is used to treat acromegaly and conditions associated with hyperprolactinemia like amenorrhea, infertility, hypogonadism, and prolactin-secreting adenomas. it is also used to prevent ovarian hyperstimulation syndrome and to treat parkinson's disease. since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal but the evidence for this use is poor. a quick-release formulation of bromocriptine, cycloset, is also used to treat type 2 diabetes. when administered within 2 hours of awakening, it increases hypothalamic dopamine level and as a result decreases hepatic glucose production. it therefore acts as an adjunct to diet and exercise to improve glycemic control. side effects most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre. 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. 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 receptors). it should be understood, however, that the greater affinity bromocriptine and many similar antiparkinson's drugs have for the d2s receptor form (considered to be mostly present at inhibitory d2 autoreceptor locatations) relative to the d2l form, sufficiently low partial agonist activity (ie where a molecule binding to a receptor induces limited effects while preventing a stronger ligand like dopamine from binding), and, possibly, the functional selectivity of a particular drug may generate antidopaminergic effects that are more similar than oppositional in nature to antipsychotics. pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of parkinson's disease. 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 estimated to range between 0.005% and 0.04%. additional safety precautions and stricter prescribing rules were suggested based on the data. it is a bile salt export pump inhibitor. after long-term use of dopamine agonists, a withdrawal syndrome may occur during dose reduction or discontinuation with the following possible side effects: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. for some individuals, these withdrawal symptoms are short-lived and they make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years. pharmacology pharmacodynamics bromocriptine in a dopamine receptor bound conformation bromocriptine is a partial agonist of the dopamine d2 receptor. it also interacts with other dopamine receptors and with various serotonin and adrenergic receptors. bromocriptine has additionally been found to inhibit the release of glutamate by reversing the glt1 glutamate transporter. as an antagonist of the serotonin 5-ht2b receptor, bromocriptine has not been associated with cardiac valvulopathy. this is in contrast to other ergolines acting instead as 5-ht2b receptor agonists such as cabergoline and pergolide but is similar to lisuride which likewise acts as a 5-ht2b receptor antagonist. activities of bromocriptine at various sites site affinity (ki ) efficacy (emax ) action d1 692 ? ? d2s 5.0 41 partial agonist d2l 15 28 partial agonist d3 6.8 68 partial agonist d4 372 0 silent antagonist d5 537 ? ? 5-ht1a 13 72 partial agonist 5-ht1b 355 66 partial agonist 5-ht1d 11 86 partial agonist 5-ht2a 107 69 partial agonist 5-ht2b 56 0 silent antagonist 5-ht2c 741 79 partial agonist 5-ht6 33 ? ? 5-ht7 11–126 ? ? α1a 4.2 0 silent antagonist α1b 1.4 ? ? α1d 1.1 ? ? α2a 11 0 silent antagonist α2b 35 0 silent antagonist α2c 28 0 silent antagonist α2d 68 ? ? β1 589 ? ? β2 741 ? ? h1 >10,000 – – m1 >10,000 – – notes: all receptors are human except α2d-adrenergic, which is rat (no human counterpart), and 5-ht7, which is rat/mouse. 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. history bromocriptine was discovered by scientists at sandoz in 1965 and was first published in 1968; it was first marketed under the brand name parlodel. a quick-release formulation of bromocriptine was approved by the fda in 2009. society and culture brand names as of july 2017, bromocriptine was marketed under many brand names worldwide, including abergin, barlolin, brameston, brocriptin, brom, broma-del, bromergocryptine, bromergon, bromicon, bromocorn, bromocriptin, bromocriptina, bromocriptine, bromocriptine mesilate, bromocriptine mesylate, bromocriptine methanesulfonate, bromocriptini mesilas, bromocriptinmesilat, bromodel, bromokriptin, bromolac, bromotine, bromtine, brotin, butin, corpadel, cripsa, criptine, criten, cycloset, degala, demil, deparo, deprolac, diacriptin, dopagon, erenant, grifocriptina, gynodel, kirim, kriptonal, lactodel, medocriptine, melen, padoparine, palolactin, parlodel, pravidel, proctinal, ronalin, semi-brom, serocriptin, serocryptin, suplac, syntocriptine, umprel, unew, updopa, upnol b, and volbro. as of july 2017 it was also marketed as a combination drug with metformin as diacriptin-m, and as a veterinary drug under the brand pseudogravin.