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 t ...

), co-dergocrine mesilate ( BAN) 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 In chemistry, a salt or ionic compound is a chemical compound consisting of an assembly of positively charged ions ( cations) and negatively charged ions (anions), which results in a compound with no net electric charge (electrically neutral). ...

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 c ...

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

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, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

) for

Sandoz Sandoz Group AG is a Swiss company that focuses on generic pharmaceuticals and biosimilars. Prior to October 2023, it was part of a division of Novartis that was established in 2003, when Novartis united all of its generics businesses under the ...

(now part of

Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...

Medical uses

It has been used to treat

dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

and age-related cognitive impairment (such as in

Alzheimer disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with ...

), as well as to aid in recovery after

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

. 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 (also spelled hyperprolactinemia) is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. ...

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

Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...

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 (; alternatively spelled aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek word ''()'', meaning "giving a reason for" (). More completely, etiology is the study of the causes, origins ...

. 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 they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

* Dermatologic: skin

rash A rash is a change of the skin that 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, cracke ...

flushing Flushing may refer to: Places Netherlands * Flushing, Netherlands, an English name for the city of Vlissingen, Netherlands United Kingdom * Flushing, Cornwall, a village in Cornwall, England * The Flushing, a building in Suffolk, England ...

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

fibrosis Fibrosis, also known as fibrotic scarring, is the development of fibrous connective tissue in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease. Repeated injuries, ch ...

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-h ...

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

ergoline Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...

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 Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

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 chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

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 bet ...

. 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 fi ...

(MAO) levels. This results in decreased availability of

catecholamines A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, 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. ...

in the synaptic cleft. In one study, an interaction between age and hydergine treatment was observed in the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

and

cerebellum The cerebellum (: cerebella or cerebellums; 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 it or eve ...

. 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 from RNA. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) ...

s is used in

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

Society and culture

Brand names

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

References

External links

Ergoloid Mesylates

University of Maryland Medical Center

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