Ergoloid mesylates ( USAN), co-dergocrine mesilate (

BAN Ban, or BAN, may refer to: Law * Ban (law), a decree that prohibits something, sometimes a form of censorship, being denied from entering or using the place/item ** Imperial ban (''Reichsacht''), a form of outlawry in the medieval Holy Roman ...

) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the

methanesulfonate In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group o ...

salts of three dihydrogenated

ergot Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''. The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...

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 Dihydroergocristine is an ergot alkaloid. Alongside dihydroergocornine and dihydroergocryptine Dihydroergocryptine (DHEC), sold under the brand names Almirid and Cripar among others, is a dopamine agonist of the ergoline group that is used as ...

, dihydroergocornine, and alpha- and

beta-dihydroergocryptine Epicriptine or ''beta''-dihydroergocryptine is a dopamine agonist of the ergoline class. It constitutes one third of the mixture known as dihydroergocryptine, the other two thirds consisting of ''alpha''-dihydroergocryptine. The ''alpha'' differs ...

). It was developed by Albert Hofmann (the discoverer of LSD) for Sandoz (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), as well as to aid in recovery after

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. 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 (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 professi ...

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 Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...

. 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 Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

* 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, cr ...

, flushing * Ocular: blurred vision * Respiratory: nasal congestion * Possible risk of fibrosis and

ergotism Ergotism (pron. ) is the effect of long-term ergot poisoning, traditionally due to the ingestion of the alkaloids produced by the ''Claviceps purpurea'' fungus—from the Latin "club" or clavus "nail" and for "head", i.e. the purple club-head ...

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. 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 is still not clear. It stimulates

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

rgic and serotonergic 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 Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...

(MAO) levels. This results in decreased availability of

catecholamines A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a substi ...

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, a ...

and

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

. 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 acids is used in

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

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