Codergocrine Mesilate

(BAN)
Codergocrine Mesilate Chemical formula

💊 Chemical information

Codergocrina, mesilato de; Co-dergocrine Mesilate; Codergocrine, mésilate de; Co-dergocrine Mesylate; Co-dergocrine Methanesulphonate; Codergocrini mesilas; Dihydroergotoxine Mesylate; Dihydroergotoxine Methanesulphonate; Dihydrogenated Ergot Alkaloids; Ergoloid Mesylates Ergot Alkaloids; Kodergokriinimesilaatti; Ko-dergokrin Mesilat; Kodergokrinmesilat; Kodergokrin-mesylát; Kodergokrino mesilatas.
CAS — 11032-41-0 (codergocrine); 8067-24-1 (codergocrine mesilate).
ATC — C04AE01.
ATC Vet — QC04AE01.

Pharmacopoeias.

In Eur., Jpn, and US.

Ph. Eur. 6.2

(Codergocrine Mesilate). A mixture of dihydroergocornine mesilate (C 31 H 41 N 5 O 5 ,CH 4 O 3 S = 659.8), dihydroergocristine mesilate, α-dihydroergocryptine mesilate, and β-dihydroergocryptine mesilate (epicriptine mesilate). It contains 30 to 35% of dihydroergocornine, 30 to 35% of dihydroergocristine, 20 to 25% of α-dihydroergocryptine, and 10 to 13% of β-dihydroergocryptine. A white or yellowish powder. Sparingly soluble in water; sparingly soluble to soluble in alcohol; slightly soluble in dichloromethane. A 0.5% solution in water has a pH of 4.2 to 5.2. Protect from light.

USP 31

(Ergoloid Mesylates). A mixture of the methanesulfonate salts of the three hydrogenated alkaloids, dihydroergocristine, dihydroergocornine, and dihydroergocryptine, in an approximate weight ratio of 1:1:1. Dihydroergocryptine mesilate exists as a mixture of alpha- and beta-isomers. The ratio of alphato beta-isomers is not less than 1.5:1.0 and not more than 2.5:1.0. A white to off-white, microcrystalline or amorphous, practically odourless powder. Slightly soluble in water; soluble in alcohol and in methyl alcohol; sparingly soluble in acetone. A 0.5% solution in water has a pH of 4.2 to 5.2. Store in airtight containers. Protect from light.

💊 Adverse Effects

Adverse effects occasionally reported with codergocrine mesilate include abdominal cramps, nausea, vomiting, headache, blurred vision, skin rashes, nasal congestion, flushing of the skin, dizziness, bradycardia, and orthostatic hypotension. Local irritation has occurred after sublingual use.

Effects on the cardiovascular system.

Of 8 patients given codergocrine mesilate 1.5 mg three times daily for the treatment of dementia, 3 developed severe sinus bradycardia associated with general deterioration in their condition, necessitating withdrawal of the treatment.1 However, no sinus bradycardia had been seen in 40 elderly patients in whom the dose was built up to 1.5 mg three times daily over 3 weeks.2
1. Cayley ACD, et al. Sinus bradycardia following treatment with Hydergine for cerebrovascular insufficiency. BMJ 1975; 4: 384–5
2. Cohen C. Sinus bradycardia following treatment with Hydergine. BMJ 1975; 4: 581.

💊 Precautions

Codergocrine mesilate should be used with caution in patients with severe bradycardia.

💊 Pharmacokinetics

Codergocrine is rapidly absorbed from the gastrointestinal tract; peak plasma concentrations are reached in about 1 to 2 hours after an oral dose. Oral bioavailability is low; this has been attributed to incomplete absorption from the gastrointestinal tract and extensive first-pass metabolism. It is 81% bound to plasma proteins. Elimination is biphasic with a short half-life of 1.5 to 2.5 hours ( α phase) and a longer half-life of 13 to 15 hours ( β phase). Codergocrine is mainly excreted with bile in the faeces, although small amounts are eliminated in the urine as metabolites and unchanged drug.

💊 Uses and Administration

Unlike the natural ergot alkaloids, codergocrine mesilate has only limited vasoconstrictor effects. A mixture of hydrogenated ergot alkaloids, codergocrine mesilate is used as an adjunct in the symptomatic treatment of mild to moderate dementia in the elderly (see also below). It is given in oral doses of 3 or 4.5 mg daily, preferably before meals. Higher doses have also been used. It is also given sublingually in similar doses. It has been given intramuscularly, subcutaneously, or by intravenous infusion. In some countries, codergocrine mesilate has been used in the treatment of hypertension, migraine, and in peripheral vascular disease. Codergocrine esilate has been used similarly to the mesilate.

Dementia.

Codergocrine has been used for many years in dementia but its value is not established.1-3 Originally its effects were thought to be mediated through peripheral and cerebral vasodilatation but it is now classified as a metabolic enhancer.
1. Wadworth AN, Chrisp P. Co-dergocrine mesylate: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in age-related cognitive decline. Drugs Aging 1992; 2: 153–73
2. Schneider LS, Olin JT. Overview of clinical trials of Hydergine in dementia. Arch Neurol 1994; 51: 787–98
3. Olin J, et al. Hydergine for dementia. Available in The Cochrane Database of Systematic Reviews; Issu
3. Chichester: John Wiley; 2000 (accessed 13/02/06).

Erectile dysfunction.

For reference to the use of creams containing codergocrine mesilate, isosorbide dinitrate, and either aminophylline or testosterone in the treatment of erectile dysfunction, see under Glyceryl Trinitrate.

💊 Preparations

BP 2008: Codergocrine Tablets; USP 31: Ergoloid Mesylates Capsules; Ergoloid Mesylates Oral Solution; Ergoloid Mesylates Tablets.

Proprietary Preparations

Arg.: CCK†; Coplexina; Ergoxina†; Hydergina; Somoblon†; Vimotadine; Austria: Dorehydrin; Ergomed; Hydergin; Belg.: Hydergine; Ibexone; Stofilan; Braz.: Hydergine; Canad.: Hydergine; Chile: Geroplus†; Hydergina†; Cz.: Secatoxin Forte; Fin.: Artergin†; Hydergin; Fr.: Capergyl; Ergodose†; Hydergine; Ger.: Circanol†; DCCK; Defluina N†; Ergodesit; ergotox; Hydergin; Hydro-Cebral; Orphol; Sponsin; Gr.: Engestol-Hyd†; Huperloid†; Hydergine; Santamin†; Zodalin†; Hong Kong: Hydergine; Perenan†; Stofilan; Trigogine; Hung.: Redergam†; India: Cereloid; Indon.: Cirloid; Ergotika; Exergin; Fontula; Hydergin; Procere; Xepadergin; Israel: Hydergine; Ital.: Hydergina; Ischelium†; Malaysia: Beagocrine†; Headgen; Hydergine; Vasculin†; Mex.: Hydergina; Philipp.: Hydergine; Port.: Hydergine; Redergot†; Secamin†; Singapore: Headgen; Hydergine; Trigogine; Spain: Ergodilat†; Hydergina; Swed.: Hydergin; Switz.: Ergohydrine; Hydergine; Thai.: Codergine†; Helcon; Hyceral; Hydergine; Hydrine; Hymed; Naline; Perenan†; Redergin†; Togine; Trigogine; Vasculin; Vasian; Turk.: Segol; UK: Hydergine†; USA: Gerimal; Hydergine; Venez.: Astergina; Hyderan†; Hydergina†. Multi-ingredient: Arg.: CCK Flunarizina†; Difusil; Neuriclor Vascular†; Neuronal Vascular†; Reagin Vascular; Austria: Pontuc; Braz.: Vincetron†; Port.: Euvifor†; Spain: Clinadil Compositum; Piracetam Complex†.
Published October 14, 2018.