Ergoloid

Ergoloid
Combination of
Dihydroergocristine	Ergot alkaloid
Dihydroergocornine	Ergot alkaloid
alpha-Dihydroergocryptine	Ergot alkaloid
beta-Dihydroergocryptine	Ergot alkaloid
Clinical data
Other names	Co-dergocrine, dihydroergotoxine
Pregnancy; category	Contraindicated;
Routes of; administration	Oral, parenteral
ATC code	C04AE01 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	25%
Protein binding	98–99%
Metabolism	50%
Elimination half-life	3.5 hours
Identifiers
CAS Number	8067-24-1 ;
DrugBank	DB01049 ;
ChemSpider	none;
UNII	X3S33EX3KW;
ChEBI	CHEBI:59756 ;
CompTox Dashboard (EPA)	DTXSID5031428 ;
ECHA InfoCard	100.158.718
	(what is this?) (verify)

Ergoloid mesylates (USAN), co-dergocrine mesilate (BAN) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the methanesulfonate salts of three dihydrogenated ergot alkaloids (dihydroergocristine, dihydroergocornine, and alpha- and beta-dihydroergocryptine).

It was developed by Albert Hofmann (the discoverer of LSD) for Sandoz (now part of Novartis).

Medical uses

It has been used to treat dementia and age-related cognitive impairment (such as in Alzheimer disease),^[1] as well as to aid in recovery after 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.^[2]

Ergoloid Mesylate Tablets USP for sublingual use contain 1 mg of Ergoloid Mesylates USP, a mixture of the methanesulfonate salt of the following hydrogenated alkaloids: Dihydroergocornine mesylate 0.333 mg, Dihydroergocristine mesylate 0.333 mg, Dihydroergocryptine mesylate 0.333 mg.^[3]

It has been used to treat hyperprolactinemia (high prolactin levels).^[4]

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).^[5]

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 etiology.^[6] Specific drug interactions are unknown but it has been claimed that there are multiple potential interactions.^[6]

Side effects

Adverse effects are minimal. The most common include transient, dose dependent nausea and gastrointestinal disturbances,^[7] and sublingual irritation with SL tablets. Other common side effects include:^[6]^[8]

Cardiovascular: orthostatic hypotension, bradycardia
Dermatologic: skin rash, flushing
Ocular: blurred vision
Respiratory: nasal congestion
Possible risk of fibrosis and ergotism^[9]^[10] ^{[failed verification]}

As a result of the last-mentioned effects, the use of 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.^[9] However, this concern may be unnecessarily suppressing the use of ergoline medications.^[11]

Pharmacology

Mechanism of action

Despite the fact that this drug has been used in the treatment of dementia for many years, its mechanism of action is still not clear.^[7] It stimulates dopaminergic and serotonergic receptors and blocks alpha-adrenoreceptors.^[12] 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.^[13] A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO) levels.^[14] 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 hypothalamus, hippocampus and cerebellum. The hydergine effect was more pronounced in the aged group in the hypothalamus and cerebellum, and more pronounced in the adult in the 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 proteinogenic amino acids is used in biosynthesis:^[15]

Compound	Amino acid
Dihydroergocristine	Phenylalanine
Dihydroergocornine	Valine
alpha-Dihydroergocryptine	Leucine
beta-Dihydroergocryptine	Isoleucine

Society and culture

Brand names

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

References

^ Flynn BL, Ranno AE (February 1999). "Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives". The Annals of Pharmacotherapy. 33 (2): 188–197. doi:10.1345/aph.17172. PMID 10084415. S2CID 12524454.
^ Schneider LS, Olin JT (August 1994). "Overview of clinical trials of hydergine in dementia". Archives of Neurology. 51 (8): 787–798. doi:10.1001/archneur.1994.00540200063018. PMID 8042927.
^ "Ergoloid". Drugs.com. Archived from the original on 12 June 2021. Retrieved 2 August 2013.
^ Bankowski BJ, Zacur HA (June 2003). "Dopamine agonist therapy for hyperprolactinemia". Clinical Obstetrics and Gynecology. 46 (2): 349–362. doi:10.1097/00003081-200306000-00013. PMID 12808385. S2CID 29368668.
^ Olin J, Schneider L, Novit A, Luczak S (2001). "Hydergine for dementia". The Cochrane Database of Systematic Reviews (2): CD000359. doi:10.1002/14651858.CD000359. PMC 6769017. PMID 11405961.
^ ^a ^b ^c "Drugs to Treat Alzheimer's Disease". Journal of Psychosocial Nursing & Mental Health Services. 52 (4): 21–22. April 2014.
^ ^a ^b Schiff PL (October 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598. PMC 1637017. PMID 17149427.
^ Majumdar A, Mangal NS (July 2013). "Hyperprolactinemia". Journal of Human Reproductive Sciences. 6 (3): 168–175. doi:10.4103/0974-1208.121400. PMC 3853872. PMID 24347930.
^ ^a ^b "Ergot derivatives: restricted use" (PDF). WHO Drug Information. 27 (3): 225. 2013.^{[dead link]}
^ Helsen V, Decoutere L, Spriet I, Fagard K, Boonen S, Tournoy J (2013). "Ergotamine-induced pleural and pericardial effusion successfully treated with colchicine". Acta Clinica Belgica. 68 (2): 113–115. doi:10.2143/ACB.3138. PMID 23967719. S2CID 24802394.
^ Zajdel P, Bednarski M, Sapa J, Nowak G (April 2015). "Ergotamine and nicergoline - facts and myths". Pharmacological Reports. 67 (2): 360–363. doi:10.1016/j.pharep.2014.10.010. PMID 25712664. S2CID 22768662.
^ Markstein R (1985). "Hydergine: interaction with the neurotransmitter systems in the central nervous system". Journal de Pharmacologie. 16 (Suppl 3): 1–17. PMID 2869188.
^ Rowell PP, Larson BT (July 1999). "Ergocryptine and other ergot alkaloids stimulate the release of [3H]dopamine from rat striatal synaptosomes". Journal of Animal Science. 77 (7): 1800–1806. doi:10.2527/1999.7771800x. PMID 10438027.
^ Kennedy GJ, Tanenbaum S (Dec 2000). "Suicide and aging: international perspectives". The Psychiatric Quarterly. 71 (4): 345–362. doi:10.1023/a:1004636307592. PMID 11025912. S2CID 35607526.
^ Steinhilber D, Schubert-Zsilavecz M, Roth HJ (2005). Medizinische Chemie (in German). Stuttgart, Germany: Deutscher Apotheker Verlag. p. 142. ISBN 3-7692-3483-9.