Galantamine Hydrobromide

Short summary description:

• Categories/Mainstream: Active pharmaceutical ingradient
• IUPAC Name:
• (1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6(17),7,9,15-tetraen-14-ol;hydrobromide
• Botanical Source: Narcissus Pseudonarcissus bulbs
• H.S code : 29397990
• CAS number: 1953-04-4
• Molecular formula: С17Н22 BrNO3
• Molecular mass: 368.30
• Country of origin: Bulgaria

The origin of tobacco absolute

In 1959, Dimitar Paskov extracted the anticholinesterase compound from the leaves and flowers of the snow drop (Galanthus Nivalis), an alkaloid named galantamine. Isolated in its pure form, this compound was named Nivalin. The discovery of the properties of the snow drop occurred by chance when Dr. Paskov noticed improvement in a girl suffering from polio, who unintentionally drank water from a cup with cinquefoil left on the table next to her bed. Today, the bulbs of narcissus grown in the Netherlands are used to extract this valuable substance for combating multiple sclerosis.

Technological process

The extraction of the active substance involves more than 20 individual technological stages carried out in 5 production buildings. According to internal procedures, the delivery of narcissus bulbs is done by pre-approved suppliers of the raw material. Upon arrival, a quality control department takes samples and analyzes the bulbs in the company's physicochemical laboratory to ensure compliance with a set of characteristics that define the quality of the raw material. The ground bulbs are processed with solvents to extract the raw substance. The final product, Galantamine Hydrobromide, undergoes multiple purifications in conditionally clean zones. Testing is conducted at each key stage of the product's production to verify the adequacy of the conducted technological process. The product is analyzed according to the monograph in Ph. Eur. The primary packaging consists of an aluminum bag placed in an aluminum barrel. Traceability from the field in the Netherlands to the company's warehouse is 100% traceable.

Properties

Originally discovered in the 1940s from Galanthus nivalis, galantamine serves as a potent, long acting, and selective acetylcholinesterase inhibitor. This enzyme plays a crucial role in acetylcholine degradation at neuromuscular junctions, peripheral and central cholinergic synapses, and parasympathetic target organs (Fulton and Benfield, 1996; Wilcock and Wilkinson, 1997). Bulgarian and Russian researchers first employed galantamine hydrobromide in the 1950s for various clinical purposes, including post-surgery reversal of tubocurarine-induced muscle relaxation, treatment of post-polio paralysis, myasthenia gravis, neuromuscular diseases, and traumatic brain injuries (Bores and Kosley, 1996; Radicheva et al., 1996).

In addition to its clinical applications, galantamine exhibits mild analeptic properties, analgesic strength comparable to morphine, and, when used in eye drops, reduces intraocular pressure. Soviet research in 1972 demonstrated galantamine’s ability to reverse scopolamine-induced amnesia in mice, a finding later confirmed in humans in 1976. Despite this, its application in Alzheimer’s disease only gained traction in 1986, long after the establishment of the cholinergic hypothesis (Allain et al., 1997).

While earlier acetylcholinesterase inhibitors like physostigmine and tacrine had limitations, galantamine hydrobromide stands out with superior pharmacological profiles and increased tolerance (Ezio, 1998; Herman and Mucke, 1997a; Kewitz, 1997; Nordberg and Svensson, 1998; Rainer, 1997a). From a clinician’s perspective, galantamine represents a reasonable approach to the ideal concept of symptomatic Alzheimer’s disease therapy (Rainer, 1997b; Wilcock and Wilkinson, 1997).

The effects of the substance on the human organism are about described as follows:

• Powerful analgesic as potent as morphine.
• Anticonvulsive.
• Hypotensive.
• Inducer of hypothermia in rats.
• Acetylcholinesterase inhibitor with peripheral and central pharmacological effects.
• Highly selective for acetylcholinesterase versus butyrylcholinesterase (more than 50-fold greater)
• Attenuates or reverses cognitive deficits induced by drugs and lesions in animal models.
• Acts as a noncompetitive nicotinic receptor agonist.

Combines both physostigmine and neostigmine properties:

• Like physostigmine, reverses opioid-induced respiratory depression but not the concomitant analgesia
• Like neostigmine, antagonizes muscle paralysis induced by d-tubocurarine, also antagonizes the ganglionic blockade and increases the contraction response.
• As hydrobromide has shown several central and peripheral effects:
• Has central effects such as antagonism of the respiratory depressant effect of morphine-like compounds.
• Can penetrate the blood-brain barrier and is used in the treatment of the central effects of scopolamine (hyoscine) intoxication. It has certain advantages over physostigmine for this purpose.

Main chemical constituents:

Physicochemical characteristics