U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Showing 11 - 20 of 45 results

alpha-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. Human intake of high doses of alpha-Solanine has led to acute intoxication, in severe cases coma and death. The ratio of a-solanine to a-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. alpha-Solanine can inhibit cholinesterase, disrupt cell membranes, and cause birth defects. Some studies suggests that the toxic mechanism of solanine is caused by the chemical's interaction with mitochondrial membranes. Experiments show that solanine exposure opens the potassium channels of mitochondria, decreasing their membrane potential. This, in turn, leads to K+ being transported from the mitochondria into the cytoplasm, and this increased concentration of K+ in the cytoplasm triggers cell damage and apoptosis.
Chelidonine is the major alkaloid component of Chelidonium majus. Chelidonine is an isolate of Papaveraceae with acetylcholinesterase and butyrylcholinesterase (a nonspecific cholinesterase) inhibitory activity. It showed strong cytotoxicity in cancer cells. While several modes of death have been identified, most of anti-cancer attempts have focused on stimulation of cells to undergo apoptosis. Chelidonine seems to trigger multiple mechanisms in MCF-7 breast cancer cells. It induces both apoptosis and autophagy modes of cell death in a dose dependent manner. Alteration of expression levels of bax/bcl2, and dapk1a by increasing concentration of chelidonine approves switching the death mode from apoptosis induced by very low to autophagy by high concentrations of this compound. On the other hand, submicromolar concentrations of chelidonine strongly suppressed telomerase at both enzyme activity and hTERT transcriptional level. Long exposure of the cells to 50 nanomolar concentration of chelidonine considerably accelerated senescence. Altogether, chelidonine may provide a promising chemistry from nature to treat cancer. Chelidonine exhibits a broad spectrum of pharmacological properties, such as anti-inflammatory and antiviral activities Its biological activities and clinical applications have been extensively investigated. Especially the usage of chelidonine as an anticancer drug is very important lately. It also has profound inhibitory effects on airway inflammation, which means chelidonine can improve allergic asthma in mice and may also work for human medicine.
Tacrine is a parasympathomimetic- a reversible cholinesterase inhibitor that is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine at cholinergic synapses through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, tacrine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that tacrine alters the course of the underlying dementing process. The mechanism of tacrine is not fully known, but it is suggested that the drug is an anticholinesterase agent which reversibly binds with and inactivates cholinesterases. This inhibits the hydrolysis of acetylcholine released from functioning cholinergic neurons, thus leading to an accumulation of acetylcholine at cholinergic synapses. The result is a prolonged effect of acetylcholine. is used for the palliative treatment of mild to moderate dementia of the Alzheimer's type. Tacrine was marketed under the trade name Cognex. Because of its liver toxicity and attendant requirement for monitoring liver function, tacrine prescriptions dropped after other acetylcholinesterase inhibitors were introduced, and its use has been largely discontinued.
Chloranil is an oxidant, practically useful for dehydrogenation to aromatic and alpha,beta-desaturated carbonyl compounds. Chloranil was found to inhibit human carboxylesterases: carboxylesterase 1 and 2, acetylcholinesterase and butyrylcholinesterase. In 1950s chloranil ointment was used for the treatment of psoriasis and onychomycosis.
Status:
US Previously Marketed
Source:
Parsidol HCl by Warner /Chilcott
(1953)
Source URL:
First approved in 1953
Source:
Parsidol HCl by Warner /Chilcott
Source URL:

Class (Stereo):
CHEMICAL (RACEMIC)



Ethopropazine is an anticholinergic drug. Ethopropazine is an inhibitor of butyrylcholinesterase and non-selective muscarinic acetylcholine receptor antagonist. Ethopropazine has been used for the treatment of parkinsonism and drug-induced extrapyramidal reactions. Also It used for the symptomatic treatment of hepatolenticular degeneration and congenital athetosis.
Edrophonium is a short and rapid-acting cholinergic drug. Chemically, edrophonium is ethyl (m-hydroxyphenyl) dimethylammonium. Edrophonium is used for the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in this disease. It may also be used for evaluating emergency treatment in myasthenic crises. Because of its brief duration of action, it is not recommended for maintenance therapy in myasthenia gravis. It is also useful whenever a curare antagonist is needed to reverse the neuromuscular block produced by curare, tubocurarine, gallamine triethiodide or dimethyl-tubocurarine. It is not effective against decamethonium bromide and succinylcholine chloride. It may be used adjunctively in the treatment of respiratory depression caused by curare overdosage.
Dichlorvos is a synthetic organic chemical used as an insecticide. Dichlorvos does not occur naturally in the environment, but is manufactured by industry. Dichlorvos is sold under many trade names including Vapona®, Atgard®, Nuvan®, and Task®. It is also used as an insecticide for slow release on pest-strips for pest control in homes.  Dichlorvos is used as an anthelmintic (worming agent) for dogs, swine, and horses, as a botacide (agent that kills fly larvae) for horses, and in flea collars for dogs. In 1995, EPA proposed cancellation of dichlorvos for all home uses, and for many commercial and industrial uses.
Status:
Possibly Marketed Outside US
Source:
NCT01796730: Phase 4 Interventional Completed COPD
(2013)
Source URL:

Class (Stereo):
CHEMICAL (RACEMIC)



Bambuterol is an active precursor of the selective beta2-adrenergic agonist terbutaline. Bambuterol is the bis-N,N-dimethyl-carbamate of terbutaline. Bambuterol is a remarkably selective and potent inhibitor of cholinesterase. BAMBEC (Bambuterol hydrochloride) oral solution or tablets are indicated for the management of asthma, bronchospasm and/or reversible airways obstruction.
Status:
Possibly Marketed Outside US
Source:
Canada:TRICHLORFON
Source URL:

Class (Stereo):
CHEMICAL (RACEMIC)



Trichlorfon (Metrifonate), the organophosphorous cholinesterase inhibitor, O,O-dimethylhydroxy-2,2,2-trichlorethyl-phosphonate, has been used sporadically in the treatment of human schistosomiasis for a decade. It has selective and variable schistosomicidal activity against S. haematobium that results from its partial metabolism to a highly active anti-cholinesterase, dichlorvos. Schistosomal cholinesterase is more susceptible to this metabolite than that of the human host, but transient reductions in both plasma and erythrocyte cholinesterase activity are demonstrable at therapeutic dosage. However, despite early concerns about its potential toxicity, metrifonate is well tolerated and has been used effectively and extensively in large-scale control programmes. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD).

Showing 11 - 20 of 45 results