A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.
A benzazepine derived from norbelladine. It is found in galanthus and other amaryllidaceae. Galantamine is a cholinesterase inhibitor that has been used to reverse the muscular effects of gallamine triethiodide and tubocurarine, and has been studied as a treatment for Alzheimer's disease and other central nervous system disorders. [PubChem]
Top Gene Interactions
Route of Elimination: Galantamine is metabolized by hepatic cytochrome P450 enzymes, glucuronidated, and excreted unchanged in the urine. Half Life: 7 hours
For the treatment of mild to moderate dementia of the Alzheimer's type. Has also been investigated in patients with mild cognitive impairment who did not meet the diagnostic criteria for Alzheimer's disease.
- Health Effects: Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
- Route of Exposure:
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 75 mg/kg (Rat) (A308)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Neuronal acetylcholine receptor subunit alpha-2
Neuronal acetylcholine receptor subunit alpha-4
Neuronal acetylcholine receptor subunit alpha-5
Neuronal acetylcholine receptor subunit alpha-7
Neuronal acetylcholine receptor subunit beta-2
Neuronal acetylcholine receptor subunit alpha-9
Neuronal acetylcholine receptor subunit beta-4
Acetylcholine receptor subunit alpha
Acetylcholine receptor subunit beta
Acetylcholine receptor subunit delta
Acetylcholine receptor subunit epsilon
Acetylcholine receptor subunit gamma
Neuronal acetylcholine receptor subunit alpha-3
Neuronal acetylcholine receptor subunit alpha-10
Neuronal acetylcholine receptor subunit beta-3
Neuronal acetylcholine receptor subunit alpha-6
|Acetylcholinesterase||Galantamine's proposed mechanism of action involves the increase of the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase.||
Galantamine Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Epilepsy, Frontal Lobe||12.74||
|Sudden Infant Death||10.58||
|Attention deficit hyperactivity disorder||7.44||
|Sleep Wake Disorders||6.97||
|Epilepsy, Nocturnal Frontal Lobe, Type 3||6.42||
|Epilepsy, Nocturnal Frontal Lobe, Type 1||6.36||
|Renal cell carcinoma||6.02||
|Drug-Related Side Effects and Adverse Reactions||6.01|
|Cerebral Amyloid Angiopathy, App-Related||5.92|
|Cerebral hemorrhage with amyloidosis, hereditary, Dutch type||5.92||