API Nicergoline

Nicergoline More Info

Nicergoline is a semisynthetic ergot-derivative α1-adrenergic receptor antagonist that has been used clinically for more than 30 years in over 50 countries to improve cerebral blood flow and cognitive function, particularly in elderly patients with vascular or degenerative dementia.

Chemical identity

• International non-proprietary name (INN): Nicergoline

• CAS number: 27848-84-6

• Molecular formula: C₂₄H₂₆BrN₃O₃; MW = 484.39 g mol⁻¹

• Structural core: 10-methoxy-1,6-dimethyl-ergoline-8β-methanol esterified with 5-bromo-nicotinic acid.

Pharmacology & mechanism of action

• Highly selective α1A-adrenergic receptor antagonist (IC₅₀ ≈ 0.2 nM in vitro), with minimal affinity for α2- or β-adrenoceptors.

• Induces peripheral and cerebral vasodilation by blocking postsynaptic α1-receptors on vascular smooth muscle, thereby lowering vascular resistance and increasing arterial inflow.

• Enhances cerebral oxygen and glucose utilization, stimulates acetylcholine-mediated neurotransmission, increases dopamine turnover, and promotes nerve growth factor expression in the aging brain.

• Exhibits antithrombotic activity through inhibition of platelet aggregation and adhesion.

Therapeutic indications (approved & clinical use)

• Cognitive impairment of vascular or degenerative origin (e.g., Alzheimer’s disease, multi-infarct dementia), especially for memory, attention and executive function deficits.

• Acute and chronic peripheral vascular disorders such as Raynaud’s syndrome, arteriopathy of the extremities, and diabetic micro-angiopathy.

• Vertigo, migraine, and occlusive cerebrovascular events (adjuvant therapy).

Dosage forms & regimens

• Oral tablets: 10 mg (white) and 30 mg (yellow).

• Parenteral (lyophilized powder for injection): 2 mg, 4 mg, or 8 mg vials for i.v. or i.m. use.

• Typical adult oral dose: 30–60 mg daily in divided doses; long-term treatment is often required for cognitive benefits.

Pharmacokinetics

• Rapidly absorbed after oral dosing; peak plasma levels reached within ~1 h in dogs (comparable data in humans).

• Extensive first-pass hepatic metabolism; active and inactive metabolites.

• Terminal half-life allows once- or twice-daily administration; steady-state plasma concentrations are achieved after 12–15 days of repeated dosing.

Safety profile

• Generally well tolerated.

• Most frequent adverse effects: mild hypotension, dizziness, flushing, gastrointestinal upset, drowsiness or insomnia.

• Contra-indicated in recent myocardial infarction, acute bleeding, severe bradycardia, hypotension, and known hypersensitivity to ergot derivatives.

Drug interactions

• Additive vasodilation when combined with other antihypertensives or vasodilators.

• May antagonize the sedative effect of α2-agonists such as xylazine; discontinue 24 h prior to anesthesia with such agents.

In summary, nicergoline is an ergoline-based α1-adrenergic blocker that improves cerebral perfusion and neuronal metabolism, making it a valuable option in the management of cognitive decline associated with cerebrovascular insufficiency and neurodegenerative disorders.