View source for Chemistry:Ergoloid

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 477511114
| image = Ergoloid skeletal.svg
| type = combo
| component1 = Dihydroergocristine
| class1 = [[Biology:Ergot|Ergot]] [[Chemistry:Alkaloid|alkaloid]]
| component2 = Dihydroergocornine
| class2 = Ergot alkaloid
| component3 = alpha-Dihydroergocryptine
| class3 = Ergot alkaloid
| component4 = beta-Dihydroergocryptine
| class4 = Ergot alkaloid

<!-- Clinical data -->
| tradename = 
| pregnancy_category = Contraindicated
| legal_status = Rx-only
| routes_of_administration = Oral, parenteral

<!-- Pharmacokinetic data -->
| bioavailability = 25%
| protein_bound = 98–99%
| metabolism = 50%
| elimination_half-life = 3.5 hours

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 8067-24-1
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = X3S33EX3KW
| ATC_prefix = C04
| ATC_suffix = AE01
| ATC_supplemental = 
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| PubChem = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01049
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 59756
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 
| synonyms = Co-dergocrine, dihydroergotoxine
<!-- Chemical data -->
}}

'''Ergoloid mesylates''' (USAN), '''co-dergocrine mesilate''' ([[Chemistry:British Approved Name|BAN]]) or '''dihydroergotoxine mesylate''', trade name '''Hydergine''', is a mixture of the [[Chemistry:Mesylate|methanesulfonate]] [[Chemistry:Salt|salts]] of three [[Chemistry:Hydrogenation|dihydrogenated]] [[Biology:Ergot|ergot]] [[Chemistry:Alkaloid|alkaloid]]s ([[Chemistry:Dihydroergocristine|dihydroergocristine]], [[Chemistry:Dihydroergocornine|dihydroergocornine]], and alpha- and beta-dihydroergocryptine).

It was developed by Albert Hofmann (the discoverer of [[Chemistry:LSD|LSD]]) for Sandoz (now part of [[Company:Novartis|Novartis]]).

==Medical uses==
It has been used to treat [[Medicine:Dementia|dementia]] and age-related cognitive impairment (such as in Alzheimer disease),<ref name="pmid10084415">{{cite journal | vauthors = Flynn BL, Ranno AE | title = Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives | journal = The Annals of Pharmacotherapy | volume = 33 | issue = 2 | pages = 188–197 | date = February 1999 | pmid = 10084415 | doi = 10.1345/aph.17172 | s2cid = 12524454 }}</ref> as well as to aid in recovery after [[Medicine:Stroke|stroke]].

A systematic review published in 1994 found little evidence to support the use of ergoloid mesylates, concluding only that potentially effective doses may be higher than those currently approved in dementia treatment.<ref>{{cite journal | vauthors = Schneider LS, Olin JT | title = Overview of clinical trials of hydergine in dementia | journal = Archives of Neurology | volume = 51 | issue = 8 | pages = 787–798 | date = August 1994 | pmid = 8042927 | doi = 10.1001/archneur.1994.00540200063018 }}</ref>

Ergoloid Mesylate Tablets USP for sublingual use contain 1&nbsp;mg of Ergoloid Mesylates USP, a mixture of the methanesulfonate salt of the following hydrogenated alkaloids: Dihydroergocornine mesylate 0.333&nbsp;mg, Dihydroergocristine mesylate 0.333&nbsp;mg, Dihydroergocryptine mesylate 0.333&nbsp;mg.<ref>{{cite web | title = Ergoloid | work = Drugs.com | url = https://www.drugs.com/pro/ergoloid.html | access-date = 2 August 2013 }}</ref>

It has been used to treat hyperprolactinemia (high prolactin levels).<ref name="pmid12808385">{{cite journal | vauthors = Bankowski BJ, Zacur HA | title = Dopamine agonist therapy for hyperprolactinemia | journal = Clinical Obstetrics and Gynecology | volume = 46 | issue = 2 | pages = 349–362 | date = June 2003 | pmid = 12808385 | doi = 10.1097/00003081-200306000-00013 | s2cid = 29368668 }}</ref>

The use of ergoloid alkaloids for dementia has been surrounded with uncertainties. In 2000, a systematic Cochrane review concluded that hydergine was well tolerated and showed significant treatment effects when assessed by either global ratings or comprehensive rating scales. The small number of available trials for analysis, however, limited the ability to demonstrate statistically significant moderating effects in certain subgroups (e.g. younger age, higher dosage, Alzheimer disease).<ref>{{cite journal | vauthors = Olin J, Schneider L, Novit A, Luczak S | title = Hydergine for dementia | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD000359 | date = 2001 | pmid = 11405961 | pmc = 6769017 | doi = 10.1002/14651858.CD000359 }}</ref>

==Contraindications==
Ergoloid is contraindicated in individuals who have previously shown hypersensitivity to the drug. They are also contraindicated in patients who have psychosis, acute or chronic, regardless of [[Philosophy:Etiology|etiology]].<ref name=psychnurse>{{Cite journal | title = Drugs to Treat Alzheimer's Disease | date = April 2014 | journal = Journal of Psychosocial Nursing & Mental Health Services | volume = 52 | issue = 4 | pages = 21–22}}</ref> Specific drug interactions are unknown but it has been claimed that there are multiple potential interactions.<ref name=psychnurse/>

==Side effects==
Adverse effects are minimal. The most common include transient, dose dependent nausea and gastrointestinal disturbances,<ref name= "Schiff_2006" /> and sublingual irritation with SL tablets. Other common side effects include:<ref name=psychnurse/><ref>{{cite journal | vauthors = Majumdar A, Mangal NS | title = Hyperprolactinemia | journal = Journal of Human Reproductive Sciences | volume = 6 | issue = 3 | pages = 168–175 | date = July 2013 | pmid = 24347930 | pmc = 3853872 | doi = 10.4103/0974-1208.121400 | doi-access = free }}</ref>

* Cardiovascular: [[Medicine:Orthostatic hypotension|orthostatic hypotension]], [[Medicine:Bradycardia|bradycardia]]
* Dermatologic: skin rash, flushing
* Ocular: blurred vision
* Respiratory: nasal congestion
* Possible risk of [[Medicine:Fibrosis|fibrosis]] and [[Medicine:Ergotism|ergotism]]<ref name=who>{{cite journal | title = Ergot derivatives: restricted use | date = 2013 | journal = WHO Drug Information | volume = 27 | issue = 3 | pages = 225 | url = http://apps.who.int/medicinedocs/documents/s21014en/s21014en.pdf }}{{dead link|date=December 2021|bot=medic}}{{cbignore|bot=medic}}</ref><ref>{{cite journal | vauthors = Helsen V, Decoutere L, Spriet I, Fagard K, Boonen S, Tournoy J | title = Ergotamine-induced pleural and pericardial effusion successfully treated with colchicine | journal = Acta Clinica Belgica | volume = 68 | issue = 2 | pages = 113–115 | year = 2013 | pmid = 23967719 | doi = 10.2143/ACB.3138 | s2cid = 24802394 | url = https://lirias.kuleuven.be/handle/123456789/420021 }}</ref> {{Failed verification | reason = not every ergoline is associated with fibrosis|date=March 2018}}

As a result of the last-mentioned effects, the use of [[Chemistry:Ergoline|ergoline]] derivatives for the treatment of blood circulation disorders, memory problems, sensation problems and the treatment of migraine is no longer permitted in some EU countries because the risks are believed to outweigh any benefits.<ref name=who/>  However, this concern may be unnecessarily suppressing the use of ergoline medications.<ref>{{cite journal | vauthors = Zajdel P, Bednarski M, Sapa J, Nowak G | title = Ergotamine and nicergoline - facts and myths | journal = Pharmacological Reports | volume = 67 | issue = 2 | pages = 360–363 | date = April 2015 | pmid = 25712664 | doi = 10.1016/j.pharep.2014.10.010 | s2cid = 22768662 }}</ref>

==Pharmacology==

===Mechanism of action===
Despite the fact that this drug has been used in the treatment of dementia for many years, its [[Chemistry:Mechanism of action|mechanism of action]] is still not clear.<ref name="Schiff_2006">{{cite journal | vauthors = Schiff PL | title = Ergot and its alkaloids | journal = American Journal of Pharmaceutical Education | volume = 70 | issue = 5 | pages = 98 | date = October 2006 | pmid = 17149427 | pmc = 1637017 | doi = 10.5688/aj700598 }}</ref> It stimulates [[Biology:Dopamine|dopamine]]rgic and [[Chemistry:Serotonin|serotonergic]] receptors and blocks alpha-adrenoreceptors.<ref name="pmid2869188">{{cite journal | vauthors = Markstein R | title = Hydergine: interaction with the neurotransmitter systems in the central nervous system | journal = Journal de Pharmacologie | volume = 16 | issue = Suppl 3 | pages = 1–17 | year = 1985 | pmid = 2869188 }}</ref>  Current studies imply that the major effect of hydergine may be the modulation of synaptic neurotransmission rather than solely increasing blood flow as was once thought.<ref name="Rowell_1999">{{cite journal | vauthors = Rowell PP, Larson BT | title = Ergocryptine and other ergot alkaloids stimulate the release of [3H]dopamine from rat striatal synaptosomes | journal = Journal of Animal Science | volume = 77 | issue = 7 | pages = 1800–1806 | date = July 1999 | pmid = 10438027 | doi = 10.2527/1999.7771800x }}</ref> A prominent feature that accompanies aging is an increase in [[Biology:Monoamine oxidase|monoamine oxidase]] (MAO) levels.<ref>{{cite journal | vauthors = Kennedy GJ, Tanenbaum S | title = Suicide and aging: international perspectives | journal = The Psychiatric Quarterly | volume = 71 | issue = 4 | pages = 345–362 | date = Dec 2000 | pmid = 11025912 | doi = 10.1023/a:1004636307592 | s2cid = 35607526 }}</ref>  This results in decreased availability of catecholamines in the synaptic cleft. In one study, an interaction between age and hydergine treatment was observed in the [[Biology:Hypothalamus|hypothalamus]], [[Biology:Hippocampus|hippocampus]] and [[Biology:Cerebellum|cerebellum]]. The hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the adult in the [[Biology:Hippocampus|hippocampus]]. These findings imply that increased brain MAO activity in aging can be modified by hydergine treatment in some brain regions.

==Chemistry==
The four constituents differ only in which of four [[Chemistry:Proteinogenic amino acid|proteinogenic amino acid]]s is used in [[Biology:Biosynthesis|biosynthesis]]:<ref>{{ cite book | title = Medizinische Chemie | page = 142 | vauthors = Steinhilber D, Schubert-Zsilavecz M, Roth HJ | publisher = Deutscher Apotheker Verlag | location = Stuttgart, Germany | year = 2005 | isbn = 3-7692-3483-9 | language = de }}</ref>

{| class="wikitable"
|-
! Compound !! Amino acid
|-
| Dihydroergocristine || [[Chemistry:Phenylalanine|Phenylalanine]]
|-
| Dihydroergocornine || [[Chemistry:Valine|Valine]]
|-
| alpha-Dihydroergocryptine || [[Chemistry:Leucine|Leucine]]
|-
| beta-Dihydroergocryptine || [[Chemistry:Isoleucine|Isoleucine]]
|}

==Society and culture==

===Brand names===
Brand names include Hydergine, Hydergina, Gerimal, Niloric, Redizork, Alkergot, Cicanol, Redergin, and Hydrine.

== References ==
{{Reflist}}

== External links ==
* [http://www.umm.edu/drug/notes/Ergoloid-mesylates-By-mouth.htm Ergoloid Mesylates] ([http://www.umm.edu/ University of Maryland Medical Center])
* [https://www.mayoclinic.org/drugs-supplements/ergoloid-mesylates-oral-route-sublingual-route/description/drg-20063714 Ergoloid Mesylates] ([https://www.mayoclinic.org/ Mayo Foundation for Medical Education and Research (MFMER).])

{{Navboxes
| title = Medical uses
| titlestyle = background:#ccccff
| list1 = 
{{Anti-dementia drugs}}
{{Peripheral vasodilators}}
{{Prolactin inhibitors and anti-inflammatory products for vaginal administration}}
}}
{{Navboxes
| title = [[Chemistry:Pharmacodynamics|Pharmacodynamics]]
| titlestyle = background:#ccccff
| list1 = 
{{Adrenergic receptor modulators}}
{{Dopamine receptor modulators}}
{{GABAA receptor positive allosteric modulators}}
{{Serotonin receptor modulators}}
}}
{{Ergolines}}

[[Category:Drugs with unknown mechanisms of action]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:Lactams]]
[[Category:Lysergamides]]
[[Category:Nootropics]]
[[Category:Oxazolopyrrolopyrazines]]

{{Sourceattribution|Ergoloid}}