Ergoloid Mesylates (Monograph)

Drug class: Non-selective alpha-Adrenergic Blocking Agents
- Hydrogenated Ergot Alkaloids
- Ergot Alkaloids
VA class: CN105
CAS number: 8067-24-1

Medically reviewed by Drugs.com on Dec 23, 2024. Written by ASHP.

Introduction

Ergoloid mesylates is an equiproportional mixture of the mesylate salts of the hydrogenated derivatives of 3 naturally occurring ergot alkaloids.

Uses for Ergoloid Mesylates

Dementia

Ergoloid mesylates has been used for the relief of signs and symptoms of idiopathic decline in mental capacity (e.g., mood, self-care, motivation, sociability, cognitive skills) in geriatric individuals.¹⁰⁵ Approved for use in 1949, ergoloid mesylates was once widely used as a cerebral vasodilator to counteract cerebrovascular insufficiency and/or cerebral arteriosclerosis (“hardening of the arteries”), which were believed at the time to cause cognitive deficits consistent with current definitions of dementia.^{106 109 111} With the advent of more precise diagnostic criteria for dementia and mounting evidence supporting other etiologic hypotheses, however, ergoloid mesylates has been largely abandoned in favor of more effective agents (e.g., cholinesterase inhibitors).^{106 107 108 109 110 111}

Efficacy of ergoloid mesylates is difficult to assess because individual studies use different signs and symptoms for evaluation, the etiology of these signs and symptoms is unknown, and the signs and symptoms are not specific for any disease or age. Results of several analyses of pooled data from randomized, controlled studies in patients with symptoms consistent with dementia indicate that ergoloid mesylates is more effective than placebo.^{106 107} However, the magnitude of improvement usually has been modest, particularly in patients with possible Alzheimer's disease,¹⁰⁹ and the value of the drug has not been clearly established.^{106 107} In addition, specific traits or conditions, if any, that might predict the likelihood of response to therapy with ergoloid mesylates have not been clearly identified.^{105 106}

There also is no convincing evidence that the drug alters sclerosis of cerebral arteries or improves the physical changes associated with aging. Efforts to improve nutrition along with psychological support to diminish feelings of loneliness and the psychological effects of idleness are the most valuable measures in the rehabilitation of the elderly.

Ergoloid Mesylates Dosage and Administration

Administration

Ergoloid mesylates is administered orally. The drug also has been administered sublingually, but a sublingual dosage form of the drug no longer is commercially available in the US.

Dosage

Dementia

The usual dosage of ergoloid mesylates is 1 mg 3 times daily.¹⁰⁵ Therapeutic response to ergoloid mesylates is usually gradual, and beneficial effects may not be observed until after 3–4 weeks of therapy.¹⁰⁵

The optimum dosage of ergoloid mesylates has not been established, but dosage has ranged from 1.5–12 mg daily.¹⁰² Some clinicians suggest a dosage of at least 6 mg daily and recommend a treatment period of 6 months to ensure an adequate trial of therapy with the drug.¹⁰² If treatment is considered beneficial and worth continuing, use of a lower dosage may be attempted; if no benefit is evident, the drug should be discontinued.¹⁰²

Cautions for Ergoloid Mesylates

Adverse Effects

Oral or sublingual (sublingual dosage form no longer commercially available in the US) administration of ergoloid mesylates has not produced any serious adverse reactions. Sublingual irritation, rashes, increased nasopharyngeal secretions or nasal stuffiness, blurred vision, orthostatic hypotension, flushing, sinus bradycardia, lightheadedness, anorexia, transient nausea and vomiting, or other mild GI disturbances have been reported infrequently.

Precautions and Contraindications

Patients should undergo careful diagnosis before ergoloid mesylates is administered to rule out the presence of potentially reversible and treatable underlying conditions.¹⁰⁵ Particular care should be employed to rule out delirium and dementiform illness secondary to systemic disease, primary neurologic disease, or primary mood disturbance. The decision to use ergoloid mesylates therapy in the treatment of an individual with a symptomatic decline in mental capacity of unknown etiology should be continually assessed, since the patient's clinical presentation may subsequently evolve sufficiently to allow a specific diagnosis and alternative therapy. In addition, continued clinical evaluation is necessary to determine whether any initial benefit of ergoloid mesylates therapy persists with time.

Ergoloid mesylates is contraindicated in patients with acute or chronic psychosis regardless of etiology or with known hypersensitivity to the drug.¹⁰⁵

Pharmacology

Ergoloid mesylates has some peripheral α-adrenergic blocking action, but has little or no vasoconstrictor activity and no oxytocic activity. The drug usually causes peripheral vasodilation primarily due to CNS depression of vasomotor nerve activity and may cause a slight decrease in blood pressure and heart rate. A few studies have shown that the drug may improve cerebral blood flow and EEG tracings, but other studies indicate that the drug does not significantly alter cerebral blood flow. It has been postulated that ergoloid mesylates may increase oxygen utilization in the brain via stabilization of ganglion cell metabolism, thus increasing cerebral blood flow indirectly rather than by direct dilation of cerebrovascular smooth muscle. There is no conclusive evidence that ergoloid mesylates affects cerebral arteriosclerosis or cerebrovascular insufficiency.

Ergoloid Mesylates Pharmacokinetics

Absorption

Orally or sublingually (sublingual dosage form no longer commercially available in the US) administered ergoloid mesylates is rapidly absorbed. Although the metabolic fate is not completely known, ergoloid mesylates undergoes first-pass metabolism in the liver, and less than 50% of a dose reaches the systemic circulation unchanged. Following administration of a single 1-mg dose of radiolabeled ergoloid mesylates as an oral solution (no longer commercially available in the US) to fasting individuals in one study, peak plasma concentrations of total radioactivity were attained within 1.5–2.9 hours.¹⁰⁰ Following administration of a single 4.5-mg dose as an oral solution (no longer commercially available in the US) to fasting individuals in a study which utilized a sensitive assay relatively specific for unchanged drug, peak plasma concentrations of unchanged drug averaged 576 pg/mL (range: 295–1100 pg/mL) and occurred after 35 minutes (range: 15–72 minutes); additional studies with IV administration of the drug indicated that the oral bioavailability averaged about 9% (range: 5–12%).¹⁰¹ Slightly higher peak plasma concentrations result when the drug is given orally compared with sublingual administration.

Elimination

Following a single oral dose of radiolabeled ergoloid mesylates in individuals with normal renal and hepatic function in one study, plasma concentrations of total radioactivity declined in a biphasic manner with an average half-life of 4.1 hours in the initial phase and 12 hours in the terminal phase.¹⁰⁰ The elimination of unchanged drug is reportedly biphasic following oral administration in healthy individuals, with the half-life averaging 2.2 hours in the initial phase and 13.2 hours in the terminal phase.¹⁰¹

Following a single oral dose of ergoloid mesylates in individuals with normal renal and hepatic function in one study, only about 2% of the dose was excreted in urine within 96 hours; the remainder of the dose was presumably excreted in feces.¹⁰⁰

Chemistry and Stability

Chemistry

Ergoloid mesylates is an equiproportional mixture of the mesylate salts of the hydrogenated derivatives of 3 naturally occurring ergot alkaloids. The derivatives are dihydroergocornine, dihydroergocristine, and dihydroergocryptine (dihydro-α-ergocryptine and dihydro-β-ergocryptine in the proportion of 2:1). The structures of dihydroergocornine and dihydroergocryptine differ from dihydroergocristine only in having an isopropyl or an isobutyl group, respectively, in place of the phenmethyl group on the polypeptide nucleus. Ergoloid mesylates occurs as a white to off-white, practically odorless, microcrystalline or amorphous powder and is slightly soluble in water and soluble in alcohol.

Stability

Ergoloid mesylates is unstable in the presence of light, moisture, or temperatures above 30°C. Ergoloid mesylates preparations should be stored in tight, light-resistant containers at 15–30°C.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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