Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Hepatic. Cytochrome P450 1A2 is the principal isozyme involved in tacrine metabolism. The major metabolite, 1-hydroxy-tacrine (velnacrine), has central cholinergic activity. Half Life: 2 to 4 hours
- Uses/Sources: For the palliative treatment of mild to moderate dementia of the Alzheimer's type.
- 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: Overdosage with 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.
- Treatment: 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: Oral. Tacrine is rapidly absorbed. Absolute bioavailability of tacrine is approximately 17%.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Glutamate receptor ionotropic, NMDA 2B Glutamate receptor ionotropic, NMDA 2A Muscarinic acetylcholine receptor M2 Cannabinoid receptor 1 Acetylcholine receptor subunit epsilon Cholinesterase Cytochrome P450 1A2 Solute carrier family 22 member 1 Solute carrier family 22 member 2 Multidrug and toxin extrusion protein 1 Cannabinoid receptor 2 Liver carboxylesterase 1 Multidrug and toxin extrusion protein 2 Cocaine esterase Metallothionein-2 |
12871155 16248836 20047331 21599003 16279811 10375753 17218977 16860785 20361801 1507203 12725862 |
|
Acetylcholinesterase | Tacrine acts by elevating acetylcholine concentrations in the cerebral cortex by slowing the degradation of acetylcholine released by still intact cholinergic neurons. It does so by reversibly binding acetylcholinesterase. |
10513568 17145705 11101357 21435752 21216144 8558505 21798635 7707311 10732965 8709135 15878275 9435905 8064800 15771436 1507203 11425559 23041347 15715468 18181565 1552502 16420031 22795665 10821713 19374444 17822295 15633997 16570913 12166941 22023459 18605718 15658850 15603953 21873056 21459491 10024872 18047264 23199476 20684567 7636841 17850125 22503231 19726199 22243648 22185619 15317459 19422203 17944454 17181144 20575555 10052979 15887964 10210906 18640842 18479118 18232655 19856923 17154513 17902635 11495583 21417225 11752352 11689088 21920739 18786825 10375753 10208549 20817518 1738151 21570751 16722663 12620072 20545360 12725862 |
Tacrine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Diabetes Mellitus, Experimental | 28.04 |
|
Breast carcinoma | 22.71 |
|
Alzheimer's Disease | 18.68 |
|
Epilepsy | 15.05 |
|
Seizures | 14.91 |
|
Brain Injuries | 14.81 |
|
Nervous System Diseases | 14.58 |
|
Reperfusion Injury | 14.55 |
|
Diabetes Mellitus, Type 2 | 13.87 |
|
Amphetamine-Related Disorders | 13.69 | |
Amyotrophic lateral sclerosis | 13.3 |
|
Cocaine dependence | 13.29 |
|
Obesity | 13.16 |
|
Schizophrenia | 12.95 |
|
Inflammation | 12.47 |
|
Chronic obstructive pulmonary disease | 12.34 |
|
Brain Ischemia | 12.32 |
|
Liver Cirrhosis, Experimental | 12.24 |
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Autism | 12.14 |
|
Prostatic Neoplasms | 12.07 |
|