Bromocriptine is an ergot alkaloid derivative in the same chemical family as LSD. It grew out of research into ergot compounds' effects on serotonin and prolactin.[1] Pharmaceutical marketing frames it primarily as a "dopamine agonist." The cited view is that this framing understates bromocriptine's equally important antiserotonin properties, since dopamine itself is generally a serotonin antagonist.[1]

Bromocriptine
Chemical structure of bromocriptine
Chemical structure of bromocriptine
Formula C32H40BrN5O5
Class Ergot alkaloid / dopamine agonist (serotonin antagonist)
Administration Oral (tablets, capsules)
Solubility Practically insoluble in water; soluble in methanol, chloroform, ethanol
Legal status Prescription only
Brand names Parlodel, Cycloset
Bioavailability 28% (oral)
Recommended dose 2.5-15 mg/day (hyperprolactinemia); 1.6-4.8 mg/day (type 2 diabetes, as Cycloset)
Upper limit 100 mg/day (maximum across indications; varies by use)
LD50 >2000 mg/kg (rat, oral)
Ray's verdict Generally helps
A serotonin antagonist that industry marketing frames purely as a "dopamine agonist," obscuring its equally important anti-serotonin effects on prolactin, tumors, and metabolism; useful for prolactinomas, diabetes/obesity, and possibly cancer, and safer than cabergoline.

When lysergic acid derivatives came onto the pharmaceutical market, the spirit of the times caused them to be described as dopamine agonists, rather than as serotonin antagonists, but the latter would be at least as descriptive of their effects. Bromocriptine fulfills many of the requirements of being a serotonin antagonist, for example by suppressing prolactin.

— Ray Peat[2]

Research on LSD and its derivatives led to drugs such as bromocriptine, which oppose the effects of histamine and estrogen. Some of bromocriptine's effects are clearly antagonistic to serotonin, though bromocriptine is usually called a dopamine agonist; dopamine is pretty generally a serotonin antagonist.

— Ray Peat[3]

Dosing

[edit]

Dose is indication-specific:

  • General therapeutic range: 2.5-5 mg daily, sometimes up to 7.5 mg, usually started at a low dose to limit nausea and orthostatic hypotension.
  • Hyperprolactinemia / prolactinoma: The cited discussion recommends trying an antiserotonin drug such as lisuride, ondansetron, or bromocriptine when prolactin runs well above the preferred range of about 9-12 ng/mL.[4]

What would your doctors think about letting you try an antiserotonin drug, like lisuride or ondansetron or bromocriptine, now that your prolactin was measured so high? I think the prolactin should be around 9 to 12.

— Ray Peat[5]
  • Peptic ulcer (studied): 2.5 mg twice daily.[6]
  • Type 2 diabetes (Cycloset): 0.8 mg/day initially, titrated up to 1.6-4.8 mg/day, taken within 2 hours of waking.[7]
  • Metergoline comparison: 2-4 mg/day of metergoline is roughly equivalent to bromocriptine for lowering prolactin.

Structure / Chemical properties

[edit]

Bromocriptine (C32H40BrN5O5) is an ergoline / ergot alkaloid derivative, related to LSD, lisuride, cabergoline, metergoline, and methysergide. All of these are built on the indole ring that serotonin itself is based on, modified with different additives, in bromocriptine's case with bromine, to shift the molecule from a serotonin-like action toward a serotonin-antagonist one.[8] It is practically insoluble in water but soluble in methanol, chloroform, and ethanol; oral bioavailability is low, around 28%.

All of these are based on the same indole molecular structure that serotonin is, but they are tuned in a different way by additives. For example, adding bromine, bromocriptine, is one that's used to treat pituitary tumors.

— Ray Peat[9]

Function / Mechanism of action

[edit]

Dopamine D2 receptor agonist

[edit]

Bromocriptine's labeled mechanism is agonism at dopamine D2 receptors. In Syrian hamsters, this dopaminergic action inhibits seasonal fattening and improves seasonal insulin resistance: bromocriptine treatment reduced weight gain (14.9 g in controls versus -2.9 g treated) and cut the area under the glucose- and insulin-tolerance curves by 29% and 48%, without changing basal plasma glucose.[10]

Serotonin antagonist

[edit]

Bromocriptine causes non-competitive antagonism of serotonin, particularly on coronary arteries and smooth muscle. In a pharmacological study, ergotamine, dihydroergotamine, bromocriptine, lisuride, ergometrine, ketanserin, trazodone, cyproheptadine, and pizotifen all produced this same non-competitive antagonism of serotonin concentration-response curves.[11]

Prolactin inhibitor

[edit]

Dopamine agonism directly suppresses prolactin secretion from the pituitary. In Ray Peat's view, this matters beyond hyperprolactinemia because prolactin interacts with prostate cancer cells at the receptor level and increases their sensitivity to androgens by upregulating androgen receptors, making a prolactin-suppressing drug a plausible adjunct in prostate disease.[12]

Inhibits serotonin synthesis (indirect)

[edit]

Dopamine and dopaminergic drugs also have a direct inhibitory effect on serotonin synthesis, by inhibiting the enzyme tryptophan hydroxylase (TPH), which is the rate-limiting step in converting tryptophan to serotonin.[13]

Medical uses / Effects

[edit]

FDA-approved indications

[edit]

Pituitary tumors

[edit]

The cited discussion describes bromocriptine and cabergoline as curative for many prolactin-secreting pituitary tumors, and links the sharp rise in these tumors' incidence to the introduction of the birth control pill, since excess estrogen drives prolactin-cell proliferation.

Many of those tumors are curable by a chemical, bromocriptine or cabergoline are two of the chemicals that have been used to shrink pituitary tumors, and those tumors became extremely common after the birth control pill was introduced, so they're basically produced by an excess of estrogen.

— Ray Peat[14]

Diabetes and obesity

[edit]

Beyond the hamster data above, the human-outcomes case for bromocriptine in type 2 diabetes comes from the Cycloset Safety Trial: a 52-week, randomized, placebo-controlled trial of roughly 3,000 patients with type 2 diabetes found significantly fewer cardiovascular events in the bromocriptine-QR group than placebo (1.8% vs. 3.2%), on top of its approved glucose-lowering effect.[7]

Peptic ulcer

[edit]

In a trial of 124 patients with endoscopically confirmed duodenal ulcer, six-month relapse rates were markedly lower on the dopaminergic drugs bromocriptine (7.7%) and amantadine (11.7%) than on the H2 blockers cimetidine (34.7%) and famotidine (25%).[6]

Cancer

[edit]

In DMBA-induced rat mammary tumors, bromocriptine lowered serum prolactin and suppressed tumor growth, comparably to tamoxifen in a head-to-head comparison.[15] This is animal data on an estrogen/prolactin-driven tumor model, not a clinical trial in humans with breast cancer, and should be read as mechanistic support for Peat's prolactin framework rather than a treatment claim.

Side / Adverse effects

[edit]

Bromocriptine is generally considered safer than cabergoline for cardiac valve risk. Both drugs are ergot derivatives that can activate the 5-HT2B receptor on heart-valve tissue, causing fibrotic thickening, but cabergoline is a substantially more potent 5-HT2B agonist.[16] In a large case-control study of Parkinson's patients, cardiac-valve regurgitation was roughly 23% more likely with pergolide and 29% more likely with cabergoline than in controls, at doses well above the range typically used for hyperprolactinemia.[17] Georgi Dinkov has argued this makes bromocriptine the safer default choice.

Cabergoline is the most potent agonist on the 5-HT2B receptor and as such has the highest risk of fibrosis of the heart and the lungs and actually the gastrointestinal tract as well. So I would be very, very careful with cabergoline. I don't think there's any reason to use cabergoline considering that a safer version known as bromocriptine is also available.

— Georgi Dinkov[18]

Brands and sources

[edit]
Brand name Form Indication
Parlodel Tablets/capsules Hyperprolactinemia, Parkinson's disease, acromegaly
Cycloset Quick-release tablets Type 2 diabetes (timed morning dosing)

Prescription required in most countries. Related ergot-family drugs include lisuride (more potent, comparable safety profile, non-hallucinogenic), metergoline (similar efficacy, also antifungal), and cabergoline (more potent but higher fibrosis risk, see Side/Adverse effects above).

Lisuride

[edit]

Lisuride is an ergot-derived dopamine agonist and serotonin antagonist. It is licensed in parts of Europe for high prolactin, stopping milk production after birth, and Parkinson's disease, is classed as a migraine-prevention drug, and is used off-label to lower prolactin.[19][20][21]

Dosing (Lisuride)

[edit]

Target prolactin range discussed alongside lisuride: 9-12.[22]

The French label for high prolactin starts at 0.1 mg in the evening, adds a second 0.1 mg dose on day 2, and settles at 0.1 mg three times daily from day 3, always with food; any increase waits 3 to 4 days.[19] To stop milk production after delivery, the label dose is 0.2 mg twice daily for 14 days, starting within the first day.[20]

For Parkinson's disease, treatment starts at 0.1 mg in the evening and rises by 0.1 mg each week, split across meals. Most people settle near 1 mg daily when lisuride is added early to levodopa, and near 2 mg daily (1 to 5 mg) later in the disease, while the levodopa dose can drop by about a fifth.[19]

Structure / Chemical properties (Lisuride)

[edit]

Lisuride (C20H26N4O, molar mass 338.4 g/mol) is an ergoline, the same four-ring indole skeleton found in LSD and bromocriptine, with a diethylurea side chain that makes it a urea derivative.[23] Medicines use the hydrogen maleate salt (C24H30N4O5, 454.5 g/mol), which is soluble enough to be given as a continuous subcutaneous infusion.[23][24]

Swallowed lisuride is absorbed quickly and completely, but most of it is broken down by the liver before reaching the circulation, leaving 10 to 22% available, with wide differences between people. Blood levels peak in about 80 minutes and the drug clears with a half-life of 2 to 3 hours, while its inactive breakdown products leave through bile and urine over about 10 hours.[19] A radiolabel study in older volunteers put oral availability at 14% and found more than 15 metabolites in urine.[25]

Function / Mechanism of action (Lisuride)

[edit]

Lisuride lowers prolactin through dopamine agonism while also blocking serotonin receptors, combining both an antiserotonin and a prolactin-lowering action in a single drug. Its labeled action is preferential stimulation of D2 dopamine receptors, mainly in the brain, which holds back prolactin release from the pituitary.[19]

Among the ergot-derived Parkinson's drugs, lisuride blocks the 5-HT2B serotonin receptor, the receptor whose activation drives drug-induced heart-valve fibrosis, while pergolide and cabergoline activate it and bromocriptine partly activates it.[26] Lisuride also activates the 5-HT2A receptor, the target of LSD, but mainly through G-protein signaling; it does not usually cause hallucinations in healthy people at routine doses, and in mice it produced few of the head twitches that mark hallucinogenic drugs.[27]

Lisuride binds strongly to nearly every dopamine, serotonin and adrenergic receptor subtype tested, a broader profile than newer non-ergot agonists such as pramipexole.[28] It activates the 5-HT1A receptor and also the 5-HT2A and 5-HT2C receptors, but not the 5-HT2B receptor.[29]

In isolated rat and guinea-pig tissue, lisuride blocked serotonin about as strongly as methysergide and blocked histamine about as strongly as diphenhydramine.[30]

Serotonin released from platelets drives skin scarring through the 5-HT2B receptor. In mice, terguride, the dihydro form of lisuride[31], reduced this scarring, and blocking 5-HT2B also shrank scarring already in place.[32] In injured mouse livers, blocking 5-HT2B let liver cells regrow and lessened established fibrosis.[33]

Medical uses / Effects (Lisuride)

[edit]

Antihistamines and some of the antiserotonin drugs (including "dopaminergic" lisuride and bromocriptine) are sometimes useful in cancer treatment, but the safe way to lower serotonin is to reduce the consumption of tryptophan, and to avoid excessive cortisol production (which mobilizes tryptophan from the muscles).

— Ray Peat[34]

In women with high prolactin and missing periods, low-dose lisuride brought prolactin back to normal in most of them, cleared all milk discharge, and restarted menstrual cycles (open study).[35] A single 0.2 mg dose lowered prolactin within an hour, and levels stayed down at the last check 5 hours later.[36]

In a 10-year randomized study of early Parkinson's disease, starting with lisuride and adding levodopa only when needed controlled disability as well as levodopa alone, while reducing and delaying motor fluctuations and dyskinesias. Severe dopamine-related side effects that ended treatment were more common on the combination.[37] In the only randomized trial against bromocriptine as an add-on to levodopa, both drugs improved motor fluctuations and parkinsonian symptoms about equally, with similar side effects.[38]

In a 6-month double-blind trial of 240 people, long-term lisuride cut the number of migraine attacks compared with placebo and was well tolerated.[39] In an open study of 420 people, attacks fell by more than half in most of them over 3 months, with nausea the most common complaint.[40]

Skin patches are meant to keep blood levels steady through the day. In a small pilot study of severe restless legs syndrome, symptoms improved on lisuride patches and worsened on placebo patches.[41] Added to existing treatment in 8 people with Parkinson's disease and unpredictable on-off swings, patches reduced motor swings over about a week, with skin irritation the main side effect.[42]

Side / Adverse effects (Lisuride)

[edit]

In a 12-week open study of 17 people with Parkinson's disease, the most frequent side effects were dry mouth, nausea, weakness, postural hypotension, and headache, which faded within 3 or 4 days as the dose was adjusted or tolerance developed.[43] A case report describes accidental overdose in a 21-month-old child.[44] No report of fibrotic heart-valve disease has been linked to lisuride, unlike pergolide, across an estimated 360,000 patient-years of use; a few cases of fibrosis elsewhere, mostly in the lungs or pleura, were found, some with other risk factors.[45]

The label lists headache, dizziness, nausea, dry mouth, tiredness and sweating at the start of treatment, mostly when the dose climbs too fast or tablets are taken without food; these usually ease with a lower dose. Sleepiness and sudden sleep attacks, sharp drops in blood pressure on standing, hallucinations and confusion (more often in older people and at high doses), and compulsive gambling or heightened sex drive are also listed. When ergot-derived agonists are used to stop milk production, high blood pressure, heart attack, seizures and stroke have rarely occurred after birth, and stopping the drug abruptly risks a neuroleptic malignant-like syndrome, so doses are tapered.[19]

Brands and sources (Lisuride)

[edit]

Lisuride is sold as the hydrogen maleate salt under the names Dopergin (Dopergine in France), Arolac, Revanil and Cuvalit, usually as 0.2 mg tablets.[23][20] It is prescription-only in the countries where it is licensed, including parts of the EU, Canada and the Middle East, and it is not approved in the United States.[46][44]

A liquid form in DMSO and ethanol supplies about 25 mcg per drop, so an 8-drop serving gives roughly 200 mcg, with 30 servings per bottle.

Lisuride
Lisuride$69.99

References

[edit]
  1. ↑ 1.0 1.1 Ray Peat, "Serotonin, depression, and aggression: the problem of brain energy," raypeat.com.
  2. ↑ Ray Peat, "Postpartum, premenstrual, and seasonal serotonin soaks," Ray Peat's Newsletter.
  3. ↑ Ray Peat, "Serotonin, depression, and aggression: the problem of brain energy," raypeat.com.
  4. ↑ Ray Peat, Prolactin email Q&A, raypeatemails.com.
  5. ↑ Ray Peat, Prolactin email Q&A, raypeatemails.com.
  6. ↑ 6.0 6.1 Sikiric P, et al. "Dopamine agonists prevent duodenal ulcer relapse," Dig Dis Sci. 1991;36(7):905-10. PMID 2070703.
  7. ↑ 7.0 7.1 Gaziano JM, Cincotta AH, O'Connor CM, et al. "Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes," Diabetes Care. 2010 Jul;33(7):1503-8. PMID 20332352.
  8. ↑ Ray Peat, interview, "Fukujima and Serotonin," Ask Your Herb Doctor (KMUD), April 15, 2011, ~34:23.
  9. ↑ Ray Peat, interview, "Fukujima and Serotonin," Ask Your Herb Doctor (KMUD), April 15, 2011, ~34:23.
  10. ↑ Luo S, Luo J, Cincotta AH. "Association of the antidiabetic effects of bromocriptine with a shift in the daily rhythm of monoamine metabolism within the suprachiasmatic nuclei of the Syrian hamster," Chronobiol Int. 2000;17(2):155-72. PMID 10757461.
  11. ↑ Ray Peat, "Autonomic systems," raypeat.com.
  12. ↑ Ray Peat, "Prostate Cancer," Ray Peat's Newsletter, 2013.
  13. ↑ Haidut, "Dopamine and dopamine agonists inhibit serotonin synthesis," Ray Peat Forum, discussion of tryptophan hydroxylase inhibition by dopaminergic drugs.
  14. ↑ Ray Peat, email Q&A, raypeatemails.com.
  15. ↑ Waseda N, Kato Y, Matsushita N, Imura H. "Effects of bromocriptine and tamoxifen on growth and hormone receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats," Endocrinol Jpn. 1983 Aug;30(4):529-35. PMID 6323151.
  16. ↑ Roth BL. "The bulky N6 substituent of cabergoline is responsible for agonism of this drug at 5-hydroxytryptamine 5-HT2A and 5-HT2B receptors and thus is a determinant of valvular heart disease," ACS Chem Neurosci. 2011. PMID 21518772.
  17. ↑ Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. "Valvular heart disease and the use of dopamine agonists for Parkinson's disease," N Engl J Med. 2007;356(1):39-46. PMID 17202454.
  18. ↑ Interview, YouTube.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 ANSM. "DOPERGINE 0,2 mg, comprimé sécable: Résumé des caractéristiques du produit" [in French]. Agence nationale de sécurité du médicament, updated 2 July 2014. Sections 4.1, 4.2, 4.4, 4.8, 4.9, 5.1, 5.2, 5.3. Oral bioavailability 10–22% from hepatic first pass; Tmax 80 ± 60 min; protein binding about 66%; Vd about 2.5 L/kg; terminal half-life 2–3 h, inactive metabolites 10 h; clearance about 0.8 L/min. Prolactin: 0.1 mg evening day 1, 0.1 mg twice day 2, 0.1 mg three times from day 3, with meals. Parkinson: start 0.1 mg evening, raise 0.1 mg per week; average 1 mg/day (0.8–1.2) early with levodopa, 2 mg/day (1–5) late.
  20. ↑ 20.0 20.1 20.2 ANSM. "AROLAC 0,2 mg, comprimé sécable: Résumé des caractéristiques du produit" [in French]. Agence nationale de sécurité du médicament, updated 30 June 2011. Section 4.2: to prevent milk production, 0.2 mg twice daily for 14 days starting within 24 h of delivery.
  21. ↑ KEGG DRUG. "D01462: Lisuride maleate". Kanehisa Laboratories. Classes: dopamine D2 receptor agonist, 5-HT1A receptor agonist, ergot alkaloid; ATC G02CB02 (prolactin inhibitor) and N02CA07 (antimigraine ergot alkaloid).
  22. ↑ "Prolactin," Ray Peat email exchange
  23. ↑ 23.0 23.1 23.2 PubChem. "Lisuride (CID 28864)" and "Lisuride maleate (CID 5282421)". National Library of Medicine. Base C20H26N4O, 338.4 g/mol; IUPAC name 3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea; maleate salt C24H30N4O5, 454.5 g/mol. Trade-name synonyms include Dopergin, Revanil, Cuvalit and Arolac.
  24. ↑ Krause W, Nieuweboer B, Ruggieri S, Stocchi F, Suchy I. "Pharmacokinetics of lisuride after subcutaneous infusion". J Neural Transm Suppl. 1988;27:71-74. doi:10.1007/978-3-7091-8954-2_8. PMID 3165439. Six Parkinson patients, 60 mcg/h subcutaneously for 2 h; steady state 0.78 ng/mL; half-life 1.4 h after stopping.
  25. ↑ Hümpel M, Krause W, Hoyer GA, Wendt H, Pommerenke G. "The pharmacokinetics and biotransformation of 14C-lisuride hydrogen maleate in rhesus monkey and in man". Eur J Drug Metab Pharmacokinet. 1984;9(4):347-357. doi:10.1007/BF03189685. PMID 6532807. Six elderly volunteers, 25 mcg IV and 200 mcg oral; oral bioavailability about 14%; IV half-lives 3 min, 16 min and 2.9 h; more than 15 urinary metabolites.
  26. ↑ Jähnichen S, Horowski R, Pertz HH. "Agonism at 5-HT2B receptors is not a class effect of the ergolines". Eur J Pharmacol. 2005;513(3):225-228. doi:10.1016/j.ejphar.2005.03.010. PMID 15862804. Porcine pulmonary artery 5-HT2B relaxation assay: pergolide and cabergoline full agonists (pEC50 8.42, 8.72), bromocriptine partial agonist (pEC50 6.86), lisuride and terguride antagonists (pKB 10.32, 8.49).
  27. ↑ Pogorelov VM, Rodriguiz RM, Roth BL, Wetsel WC. "The G protein biased serotonin 5-HT2A receptor agonist lisuride exerts anti-depressant drug-like activities in mice". Front Mol Biosci. 2023;10:1233743. doi:10.3389/fmolb.2023.1233743. PMID 37900918. Mouse study in wild-type and β-arrestin knockout mice; head twitches and retrograde walking were low in all genotypes.
  28. ↑ Millan MJ, Maiofiss L, Cussac D, et al. "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. 2002;303(2):791-804. doi:10.1124/jpet.102.039867. PMID 12388666. 21 dopamine, serotonin, adrenergic and histamine receptor subtypes; lisuride and terguride had high affinity at all sites.
  29. ↑ Newman-Tancredi A, Cussac D, Quentric Y, et al. "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. 2002;303(2):815-822. doi:10.1124/jpet.102.039883. PMID 12388668. Human cloned receptors; all eight drugs stimulated 5-HT1A; lisuride agonist at 5-HT2A and 5-HT2C; only pergolide and cabergoline were clear 5-HT2B agonists.
  30. ↑ Funaki H, Tokiyori Y, Hara K, Oshino N. "[General pharmacology of lisuride hydrogen maleate--actions on isolated organs, especially on smooth muscles]" [in Japanese]. Nihon Yakurigaku Zasshi (Folia Pharmacologica Japonica). 1982;80(5):349-365. doi:10.1254/fpj.80.349. PMID 7166281. Isolated organs: anti-5-HT ID50 11 nM (rat stomach), equipotent to methysergide; antihistamine ID50 15 nM (guinea-pig ileum), equipotent to diphenhydramine; alpha-adrenolytic ID50 64 nM (rat vas deferens). English abstract only.
  31. ↑ Krause W, Nieuweboer B, Hümpel M, et al. "Pharmacokinetics and pharmacodynamics of the ergot derivative, transdihydrolisuride, in man". Eur J Clin Pharmacol. 1984. PMID 6510462. Transdihydrolisuride is terguride.
  32. ↑ Dees C, Akhmetshina A, Zerr P, et al. "Platelet-derived serotonin links vascular disease and tissue fibrosis". J Exp Med. 2011;208(5):961-972. doi:10.1084/jem.20101629. PMID 21518801. Systemic sclerosis fibroblasts and mouse bleomycin skin-fibrosis models; terguride 0.2 and 0.6 mg/kg twice daily, cyproheptadine and the selective 5-HT2B blocker SB 204741 all reduced dermal thickening and collagen; 5-HT2B knockout mice were protected. The authors list lisuride among well-tolerated 5-HT2 inhibitors already in clinical use.
  33. ↑ Ebrahimkhani MR, Oakley F, Murphy LB, et al. "Stimulating healthy tissue regeneration by targeting the 5-HT₂B receptor in chronic liver disease". Nat Med. 2011;17(12):1668-1673. doi:10.1038/nm.2490. PMID 22120177. Mouse acute and chronic liver injury; serotonin acting on 5-HT2B in hepatic stellate cells raised TGF-β1 and held back liver-cell regrowth; a selective 5-HT2B antagonist restored regrowth and reduced pre-established fibrosis. Lisuride itself was not tested.
  34. ↑ Preventing and treating cancer with progesterone, raypeat.com
  35. ↑ Rojanasakul A, Sirimongkolkasem R, Chailurkit LO. "The efficacy of lisuride in the treatment of hyperprolactinemic amenorrhea". J Med Assoc Thai. 1990;73 Suppl 1:42-46. PMID 2351912. Open study, 13 women, 12 completed (one dropout for nausea and dizziness); prolactin normalized in 10 of 12; most took 0.2–0.4 mg/day; menses resumed within 23–141 days; 2 of 5 women seeking pregnancy conceived.
  36. ↑ Liuzzi A, Chiodini PG, Oppizzi G, et al. "Lisuride hydrogen maleate: evidence for a long lasting dopaminergic activity in humans". J Clin Endocrinol Metab. 1978;46(2):196-202. doi:10.1210/jcem-46-2-196. PMID 108287. 12 people with acromegaly given single oral doses of 0.2, 0.3 or 0.4 mg; prolactin fell from 60 min and stayed suppressed at 300 min, the last time point; 0.3 mg also blunted TRH-induced prolactin release in 6 healthy subjects.
  37. ↑ Rinne UK. "[Combination therapy with lisuride and L-dopa in the early stages of Parkinson's disease decreases and delays the development of motor fluctuations. Long-term study over 10 years in comparison with L-dopa monotherapy]" [in German]. Nervenarzt. 1999;70 Suppl 1:S19-25. doi:10.1007/s001150050585. PMID 10087526. Randomized prospective study, 90 patients with early Parkinson's disease, 10 years; few patients stayed on lisuride alone long term. English abstract only.
  38. ↑ Clarke CE, Speller JM. "Lisuride versus bromocriptine for levodopa-induced complications in Parkinson's disease". Cochrane Database Syst Rev. 2000;(2):CD001514. doi:10.1002/14651858.CD001514. PMID 10796800. Systematic review; one randomized crossover trial, 20 patients; the reviewers judged it too small for firm conclusions.
  39. ↑ Herrmann WM, Kristof M, Sastre M, Sastre M. "Preventive treatment of migraine headache with a new isoergolenyl derivative". J Int Med Res. 1978;6(6):476-482. doi:10.1177/030006057800600611. PMID 363486. Double-blind, placebo-controlled, 240 patients, 6 months.
  40. ↑ Soyka D, Frieling B. "[Lisuride for the prevention of migraine. Results of a multicenter study]" [in German]. Fortschr Med. 1989;107(35):763-766. PMID 2691377. Open multicenter study, 420 patients, 3 months; attack frequency more than halved in 61.4%; nausea 4.0%, vertigo 3.1%, drowsiness 1.4%. English abstract only.
  41. ↑ Benes H. "Transdermal lisuride: short-term efficacy and tolerability study in patients with severe restless legs syndrome". Sleep Med. 2006;7(1):31-35. doi:10.1016/j.sleep.2005.05.007. PMID 16194624. Pilot study, 10 patients; 2 weeks open-label with one or two 3 mg patches (about 7 mcg/h) every other day, then 1 week randomized lisuride (5) vs placebo (4).
  42. ↑ Woitalla D, Müller T, Benz S, Horowski R, Przuntek H. "Transdermal lisuride delivery in the treatment of Parkinson's disease". J Neural Transm Suppl. 2004;(68):89-95. doi:10.1007/978-3-7091-0579-5_10. PMID 15354393. Observational study, 8 patients with unpredictable on-off swings, patches added for up to 8 days; skin irritation in 4.
  43. ↑ Bayülkem K, Erişir K, Tuncel A, Bayülkem B. "A study on the effect and tolerance of lisuride on Parkinson's disease". Adv Neurol. 1996;69:519-530. PMID 8615174. Uncontrolled 12-week study, 17 patients; added doses 0.1–0.8 mg.
  44. ↑ 44.0 44.1 Alahmadi TA, Mujawar QM. "Lisuride toxicity in a pediatric patient". J Emerg Trauma Shock. 2013;6(2):140-142. doi:10.4103/0974-2700.110803. PMID 23723628. Case report of accidental overdose in a 21-month-old child; states licensing in Canada, the EU and Middle East countries.
  45. ↑ Hofmann C, Penner U, Dorow R, et al. "Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis". Clin Neuropharmacol. 2006;29(2):80-86. doi:10.1097/00002826-200603000-00005. PMID 16614540. Literature and adverse-drug-reaction database review by the manufacturer (Schering AG); about 360,000 patient-years; other fibrosis reports: 1 retroperitoneal, 2 pleural, 2 pulmonary, 1 interstitial pulmonary, partly with confounders.
  46. ↑ Drugs and Lactation Database (LactMed). "Lisuride". National Institute of Child Health and Human Development, NCBI Bookshelf. Not approved for marketing in the United States; approved in some countries for lactation suppression.