GALANTHAMINE HYDROBROMIDE
Galanthamine hydrobromide is an alkaloid that is isolated from the tubers of snowdrop Voronov (Galanthus Woronowii A. Los.), a family of Amaryllidaceae (Amaryllidaceae). It is also contained in other species of snowdrop of the genus Galanthus. White fine crystalline powder of bitter taste.
Structural formula
Gross formula: C17H21NO3·HBr
Purity:> 95%
Chemical name: 6H-Benzofuro (3a, 3,2-ef) (2) benzazepin-6-ol, 4a, 5,9,10,11,12-hexahydro-3-methoxy-11-methyl-, hydrobromide, ( 4aS, 6R, 8aS) -
Molecular weight: 368.28 g / mol
Latin name: Galanthamini hydrobromidum
CAS code: 1953-04-4
Pharmacological group of substance
Galanthamine: Active anticholinesterase agent, reversible inhibitor of cholinesterase.
Indications for use
• Acute poliomyelitis
• Tick-borne viral encephalitis
• Impact of poliomyelitis
• Dementia in Alzheimer's disease (G30 +)
• Encephalitis, myelitis and encephalomyelitis
• Lesions of the facial nerve
• Mononeuropathy, unspecified
• Guillain-Barre Syndrome
• Other polyneuropathies
• Myasthenia gravis and other disorders of the neuromuscular synapse
• Muscular dystrophy
• Other myopathies
• Cerebral palsy
• Disorder of autonomic nervous system, unspecified
• Atony of intestine
• Diagnosis of diseases of digestive tract
• Radiculopathy
• Neuralgia and neuritis, unspecified
• Neurogenic weakness of bladder, not elsewhere classified
• Other specified incontinence
• Trauma of nerve (nerves) of unspecified area of the body
• Poisoning by drugs and psychodysleptics [hallucinogens]
• Poisoning with drugs that act primarily on the autonomic nervous system
Pharmacological properties: Pharmacological action - anticholinesterase.
Reversibly inhibits acetylcholinesterase, enhances and prolongs the action of endogenous acetylcholine. It facilitates impulses in the cholinergic, incl. neuromuscular, synapses, enhances excitation processes in the reflex zones of the spinal cord and brain. Increases the tone of smooth and skeletal muscles, stimulates the secretion of digestive and sweat glands. Causes miosis and spasm of accommodation, lowers the intraocular pressure in closed-angle glaucoma. When injected into the conjunctival sac, it can cause temporary swelling of the conjunctiva. Penetrates through the BBB, enhances excitation processes in the central nervous system. When used in complex therapy of spastic forms of infantile cerebral palsy, it improves neuromuscular conduction, increases the contractile ability of muscles, positively influences mnestic functions. By increasing the activity of the cholinergic system, cognitive function can improve in patients with Alzheimer's dementia.
After a single oral intake of 8 mg, it is quickly absorbed from the digestive tract, bioavailability - about 90%. Eating slows down absorption (Cmax decreases by 25%), but it does not affect the completeness of absorption (AUC). Tmax is achieved after 1.2 hours.
The pharmacokinetics of galanthamine is linear in the dose range of 4-16 mg 2 times a day. Binding to plasma proteins - 18%. In whole blood, galanthamine is predominantly in shaped elements (52.7%). The ratio of galanthamine blood / plasma concentrations is 1.2. Plasma clearance - about 300 ml / min, the volume of distribution - 175 liters. The main ways of metabolism are N-oxidation, N- and O-demethylation, glucuronization and epimerization. In people with active metabolism of CYP2D6 substrates, the most important metabolic pathway is O-demethylation. The main isoenzymes of the cytochrome P450 system, involved in the metabolism of galanthamine are CYP2D6 and CYP3A4. In the plasma of people with fast and slow metabolism, the main part is unchanged galanthamine and its glucuronide. In the plasma of people with rapid metabolism, glucuronide O-desmethylgalanthamine is also found. Excretion is biphasic, final T1 / 2 - 7-8 hours. Kidney clearance - 65 ml / min (20-25% of plasma clearance). It is excreted in urine (90-97%, 18-22% of it in unchanged form within 24 hours) and feces (2.2-6.3%). After a single administration of galanthamine in the plasma of fast and slow metabolizers, none of the active metabolites (norgalanthamn, O-demethylgalanthamine and O-demethylnoghalanthamine) in unconjugated form was detected. Norgalanthamine is found in the plasma of patients after repeated administration of galanthamine (no more than 10% of the concentration of galanthamine). In patients with Alzheimer's disease, the concentration of galanthamine in blood plasma is 30-40% higher than in young healthy people. With moderate hepatic insufficiency (7-9 on the Child-Pugh scale), AUC and T1 / 2 increase by 30%. With moderately severe chronic renal insufficiency (creatinine clearance 52-104 ml / min), the plasma concentration of galanthamine is increased by 38%, with severe (creatinine clearance - 9-51 ml / min) - by 67%.