Top Gene Interactions
- 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
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
|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.||
Tacrine Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Diabetes Mellitus, Experimental||28.04||
|Nervous System Diseases||14.58||
|Diabetes Mellitus, Type 2||13.87||
|Amyotrophic lateral sclerosis||13.3||
|Chronic obstructive pulmonary disease||12.34||
|Liver Cirrhosis, Experimental||12.24||