Ergoloid mesylates (

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...

), co-dergocrine mesilate ( BAN) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the methanesulfonate

salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...

of three dihydrogenated ergot

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

s ( dihydroergocristine, dihydroergocornine, and alpha- and beta-dihydroergocryptine). It was developed by

Albert Hofmann Albert Hofmann (11 January 1906 – 29 April 2008) was a Swiss chemist known for being the first to synthesize, ingest, and learn of the psychedelic effects of lysergic acid diethylamide (LSD). Hofmann's team also isolated, named and synthesi ...

(the discoverer of

LSD Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...

) for

Sandoz Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loca ...

(now part of

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

Medical uses

It has been used to treat

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

and age-related cognitive impairment (such as in

Alzheimer disease Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...

), 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. 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. It has been used to treat

hyperprolactinemia Hyperprolactinaemia is the presence of abnormally high levels of prolactin in the blood. Normal levels average to about 13 ng/mL in women, and 5 ng/mL in men, with an upper normal limit of serum prolactin levels being 15-25 ng/mL ...

(high prolactin levels). The use of ergoloid alkaloids for dementia has been surrounded with uncertainties. In 2000, a systematic

Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...

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).

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. Specific drug interactions are unknown but it has been claimed that there are multiple potential interactions.

Side effects

Adverse effects are minimal. The most common include transient, dose dependent nausea and gastrointestinal disturbances, and sublingual irritation with SL tablets. Other common side effects include: * Cardiovascular:

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

, bradycardia * Dermatologic: skin

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

flushing Flushing may refer to: Places * Flushing, Cornwall, a village in the United Kingdom * Flushing, Queens, New York City ** Flushing Bay, a bay off the north shore of Queens ** Flushing Chinatown (法拉盛華埠), a community in Queens ** Flushin ...

* Ocular: blurred vision * Respiratory: nasal congestion * Possible risk of

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

and ergotism As a result of the last-mentioned effects, the use of

ergoline Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of thes ...

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. However, this concern may be unnecessarily suppressing the use of ergoline medications.

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 In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

is still not clear. It stimulates dopaminergic and

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

receptors and blocks alpha-

adrenoreceptors The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

. 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. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO) levels. 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 The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

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

. 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 acid Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino aci ...

s is used in biosynthesis:

Society and culture

Brand names

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

References

External links

Ergoloid MesylatesUniversity of Maryland Medical Center

Ergoloid MesylatesMayo Foundation for Medical Education and Research (MFMER).
{{Ergolines Antidementia agents Drugs with unknown mechanisms of action GABAA receptor positive allosteric modulators Lactams Lysergamides Nootropics Oxazolopyrrolopyrazines