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.[6]
A quick-release formulation of bromocriptine, Cycloset, is also used to treat type 2 diabetes.[7][8][9] 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.[10]
Side effects
Most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre.[11] 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.[12] 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).[13]Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.[14]
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.[15][16] It is a bile salt export pump inhibitor.[17]
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.[18]
Pharmacology
Pharmacodynamics
Bormocriptine in a dopamine receptor bound conformation
Notes: All receptors are human except α2D-adrenergic, which is rat (no human counterpart), and 5-HT7, which is rat/mouse.[19][25]
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 amidefunctionality.
Bromocriptine was discovered by scientists at Sandoz in 1965 and was first published in 1968; it was first marketed under the brand name Parlodel.[28][29]
A quick-release formulation of bromocriptine was approved by the FDA in 2009.[30]
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.[1]
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.[1]
^Garber AJ, Blonde L, Bloomgarden ZT, Handelsman Y, Dagogo-Jack S (2013). "The role of bromocriptine-QR in the management of type 2 diabetes expert panel recommendations". Endocrine Practice. 19 (1): 100–6. doi:10.4158/EP12325.OR. PMID23337160.
^Liang W, Gao L, Li N, Wang B, Wang L, Wang Y, et al. (October 2015). "Efficacy and Safety of Bromocriptine-QR in Type 2 Diabetes: A Systematic Review and Meta-Analysis". Hormone and Metabolic Research. 47 (11): 805–12. doi:10.1055/s-0035-1559684. PMID26332757.
^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. PMID3516579.
^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. PMID8691994.
^Todman DH, Oliver WA, Edwards RL (1990). "Pleuropulmonary fibrosis due to bromocriptine treatment for Parkinson's disease". Clinical and Experimental Neurology. 27: 79–82. PMID2129961.
^ abcdMillan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes". J Pharmacol Exp Ther. 303 (2): 791–804. doi:10.1124/jpet.102.039867. PMID12388666.
^ abcNewman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor". J Pharmacol Exp Ther. 303 (2): 805–14. doi:10.1124/jpet.102.039875. PMID12388667.
^de Leeuw van Weenen JE, Parlevliet ET, Maechler P, Havekes LM, Romijn JA, Ouwens DM, et al. (June 2010). "The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the alpha2-adrenergic receptors in beta cells". Biochemical Pharmacology. 79 (12): 1827–36. doi:10.1016/j.bcp.2010.01.029. PMID20138024.
^ abcNewman-Tancredi A, Cussac D, Quentric Y, Touzard M, Verrièle L, Carpentier N, Millan MJ (November 2002). "Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes". J Pharmacol Exp Ther. 303 (2): 815–22. doi:10.1124/jpet.102.039883. PMID12388668.
^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. PMID20599932.
^ abCavero I, Guillon JM (2014). "Safety Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy". J Pharmacol Toxicol Methods. 69 (2): 150–61. doi:10.1016/j.vascn.2013.12.004. PMID24361689.
^ abNational Institute of Mental Health. PDSP Ki Database (Internet). ChapelHill (NC): University of North Carolina. Available from: "Archived copy". Archived from the original on 2021-04-12. Retrieved 2021-04-12.((cite web)): CS1 maint: archived copy as title (link)
^DE 1926045A1, Hofmann, Albert; Flueckiger, Edward & Troxler, Franz, "Verfahren zur Herstellung einer neuen heterocyclischen Verbindung [Process for the preparation of a new heterocyclic compound]", published 1969-12-04, assigned to Sandoz AG