Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently synthesized triptans, sumatriptan derivatives, display aborting migraine activity at doses and with plasmatic maximum peak dramatically lower (20-40 times) than sumatriptan, the 5-HT like agonist, which is the original molecule. That triptans easily cross blood-brain barrier strongly supports the central theory of migraine. We recently discovered the anti-migraine prophylactic action of centrally acting anti-cholinesterase agents, that seems a further support to the central theory of migraine. Indeed, acetylcholine is an important analgesia neurotransmitter and is intertwined with 5-HT central pathways.
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PMID:Triptans. A support to the central link between serotonin and acetylcholine in migraine. 1072 Oct 55

The antinociceptive activity of donepezil, a novel cholinesterase inhibitor, was investigated in the mouse hot plate test. Donepezil (5 to 10 mg kg(-1) i.p.) induced a dose-dependent antinociception that reached its maximum effect 15 minutes after injection. Donepezil antinociception was prevented by the antimuscarinic drug scopolamine. At analgesic doses, donepezil did not alter gross animal behavior. These results indicate that donepezil is endowed by muscarinic antinociceptive properties, suggesting this compound as a potential therapeutic approach for the treatment of painful pathologies. Therefore, we investigated donepezil's effect in migraine. Donepezil (5 mg per os, evening assumption) was effective as a prophylatic agent in patients suffering from migraine with or without aura by reducing the number of hours with pain, the number of attacks, and the severity of the pain attack. The efficacy of donepezil was compared with that of the beta-blocker propranolol (40 mg bid per os), showing higher activity. Response rates of a large-sized open study devoid of entry criteria regarding migraine subtypes suggest the drug as an excellent prophylactic compound for migraine in general practice. Clinical results also indicate that the activation of the cholinergic system can represent a novel prophylactic approach to migraine.
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PMID:Central cholinergic challenging of migraine by testing second-generation anticholinesterase drugs. 1248 11

Neurologists and ophthalmologists should be familiar with the causes and treatment of visual hallucinations so that they are able to reassure patients and minimize the anguish associated with untreated visual hallucinations. Hallucinations are under-reported by patients because of the perceived psychiatric implication or because of poor insight into the unreal nature of the hallucinations. In the appropriate setting, physicians should specifically inquire about hallucinations as well as initiate medical treatment. Visual hallucinations have many etiologies and are associated with a variety of disorders. Identification of the associated disorder or cause is necessary to determine the appropriate treatment. Causes and associated disorders include ocular phenomena, migraine, seizures, visual loss (ie, release hallucinations), neurodegenerative disorders, midbrain injury, alcohol and drug effects, narcolepsy, post-traumatic stress disorder, and psychosis. Therapeutic treatment should be directed at the associated disorder or etiology. For instance, antiepileptic drugs may be appropriate for patients with irritative phenomena such as seizures and visual aura of migraine. Depending on the cause, other agents are available and include neuroleptics, cholinesterase inhibitors, and acetazolamide. Well-designed, randomized, controlled clinical trials regarding treatment of visual hallucinations associated with various disorders are lacking. Although complete resolution of visual hallucinations can be difficult, even minimal improvement may be symptomatically beneficial.
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PMID:Visual Hallucinations. 1466 72

Enhancement of the activity of cholinergic neurons has been regarded as one of the most promising methods for treating Alzheimer's disease (AD). Donepezil is a representative acetylcholinesterase inhibitor (AChEI) and is a great success among the AChEI drugs. AChEIs are being studied for other mechanisms of action, neuroprotective action, and nicotinic receptor enhancement. AD is a type of neurodegenerative disease and AChEIs have been found to be an effective anti-AD medication. AChEI can alleviate the symptoms and delay the progression of AD, but it cannot cure the disease. However, AChEIs are now the subject of a wide range of clinical studies for other diseases, for example, other types of dementia (such as Lewy body disease, cerebral vascular dementia, and Parkinson's disease dementia), and migraine. These drugs are also being studied as a combination therapy, for example, with an antioxidant, SERM, and NMDA antagonist.
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PMID:[Scope and limitations of acetylcholinesterase inhibitors]. 1533 89

Six migraine patients experienced significant topiramate-related cognitive and language dysfunction that improved with donepezil treatment and allowed uninterrupted topiramate use. These patients represent the first report of topiramate-related cognitive and language dysfunction that improved with a cholinesterase inhibitor. Although, the mechanism responsible for this effect is uncertain, cholinesterase inhibition resulting in cholinergic augmentation and enhanced cognition probably account for some if not most of the improvement.
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PMID:Donepezil treatment of topiramate-related cognitive dysfunction. 1649 46

The sphenopalatine ganglion (SPG) is the main parasympathetic ganglion that is involved in regulating cerebral vascular tone and gland secretion. SPG neurons have been implicated in some types of migraine headaches but their precise role has yet to be determined. In addition, very little information is available regarding ion channel modulation by neurotransmitters that are involved in the parasympathetic drive of SPG neurons. In this study, acute isolation of adult rat SPG neurons was developed in order to begin the electrophysiological characterization of this ganglion. Under our dissociation conditions, the average number of neurons obtained per ganglion was greater than 1200. Immunofluorescence imaging results showed positive labeling with acetylcholinesterase (AChE), confirming the parasympathetic nature of SPG neurons. On the other hand, weak tyrosine hydroxylase immunostaining was observed in these neurons. Whole-cell patch-clamp recordings revealed that most of the Ca(2+) current is carried by N-type (53%) and SNX-482 resistant R-type (30%) Ca(2+) channels. In addition, Ca(2+) currents were inhibited in a voltage-dependent manner following exposure to oxotremorine-M (Oxo-M), norepinephrine and ATP via muscarinic acetylcholine receptor 2 (M(2) AChR) subtype, adrenergic and P2Y purinergic receptors, respectively. The peptides VIP and angiotensin II failed to modulate Ca(2+) currents, suggesting that these receptors are not present on the SPG soma or do not couple to Ca(2+) channels. In summary, our data suggest that the Ca(2+) current inhibition mediated by Oxo-M, NE and ATP in adult rat SPG neurons plays an integral part in maintaining parasympathetic control of cranial functions.
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PMID:Electrophysiological and immunofluorescence characterization of Ca(2+) channels of acutely isolated rat sphenopalatine ganglion neurons. 1750 62

The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer's disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.
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PMID:The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. 1806 9

Mitochondrial disorders, in particular respiratory chain diseases (RCDs), present either as single organ problem or as multi-system disease. One of the most frequently affected organs in RCDs, in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs include epilepsy, stroke-like episodes, migraine-like headache, ataxia, spasticity, movement disorders, psychosis, demyelination, calcification, but also dementia. Cognitive impairment may be a feature of syndromic as well as non-syndromic RCDs. Syndromic RCDs associated with cognitive impairment include MELAS, KSS, Leigh syndrome, and many others. RCDs with cognitive decline not only result from mtDNA mutations but also from mutations in nuclear genes. At onset there is often no general intellectual deterioration in these patients but specific cognitive deficits, particularly in the visual construction, attention, abstraction, or flexibility. Diagnosis of cognitive impairment from RCDs is based on neuropsychological testing, imaging studies, including MRI, PET, SPECT, or MR-spectroscopy, CSF investigations, or electroencephalography. Therapeutic strategies for dementia in RCDs rely on symptomatic measures. Only single patients may profit from cholinesterase inhibitors or memantine, antioxidants, vitamins, or other substitutes. Overall, cognitive decline in RCDs (mitochondrial dementia) needs to be included in the differentials of dementia.
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PMID:Cognitive decline as a manifestation of mitochondrial disorders (mitochondrial dementia). 1857 95

The organ most frequently affected in mitochondrial disorders, particularly respiratory chain diseases (RCDs), in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs comprise stroke-like episodes, epilepsy, migraine, ataxia, spasticity, movement disorders, psychiatric disorders, cognitive decline, or even dementia (mitochondrial dementia). So far mitochondrial dementia has been reported in MELAS, MERRF, LHON, CPEO, KSS, MNGIE, NARP, Leigh syndrome, and Alpers-Huttenlocher disease. Mitochondrial dementia not only results from mutations in the mitochondrial genome but also from mutations in nuclear genes, such as POLG, thymidine kinase 2, or DDP1. Often mitochondrial dementia starts with specific cognitive deficits, particularly in visual construction, attention, abstraction, or flexibility but without a general intellectual deterioration. Cognitive impairment in RCDs is diagnosed upon neuropsychological testing, imaging studies, such as MRI, PET, or MR-spectroscopy, CSF-investigations, or electroencephalography. Therapy of mitochondrial dementia relies on symptomatic measures. Only single patients profit from cholinesterase inhibitors or memantine, antioxidants, vitamins, coenzyme-Q, or other substitutes. Overall, mitochondrial dementia is an important differential of dementias and should be considered in patients with multi-system disease.
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PMID:Mitochondrial disorders, cognitive impairment and dementia. 1926 75

The C. elegans eat-6 gene encodes a Na(+), K(+)-ATPase alpha subunit and is a homolog of the familial hemiplegic migraine candidate gene FHM2. Migraine is the most common neurological disorder linked to serotonergic dysfunction. We sought to study the pathophysiological mechanisms of migraine and their relation to serotonin (5-HT) signaling using C. elegans as a genetic model. In C. elegans, exogenous 5-HT inhibits paralysis induced by the acetylcholinesterase inhibitor aldicarb. We found that the eat-6(ad467) mutation or RNAi of eat-6 increases aldicarb sensitivity and causes complete resistance to 5-HT treatment, indicating that EAT-6 is a component of the pathway that couples 5-HT signaling and ACh neurotransmission. While a postsynaptic role of EAT-6 at the bodywall NMJs has been well established, we found that EAT-6 may in addition regulate presynaptic ACh neurotransmission. We show that eat-6 is expressed in ventral cord ACh motor neurons, and that cell-specific RNAi of eat-6 in the ACh neurons leads to hypersensitivity to aldicarb. Electron microscopy showed an increased number of synaptic vesicles in the ACh neurons in the eat-6(ad467) mutant. Genetic analyses suggest that EAT-6 interacts with EGL-30 Galphaq, EGL-8 phospholipase C and SLO-1 BK channel signaling to modulate ACh neurotransmission and that either reduced or excessive EAT-6 function may lead to increased ACh neurotransmission. Study of the interaction between eat-6 and 5-HT receptors revealed both stimulatory and inhibitory 5-HT inputs to the NMJs. We show that the inhibitory and stimulatory 5-HT signals arise from distinct 5-HT neurons. The role of eat-6 in modulation of excitatory neurotransmission by 5-HT may provide a genetic explanation for the therapeutic effects of the drugs targeting 5-HT receptors in the treatment of migraine patients.
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PMID:A homolog of FHM2 is involved in modulation of excitatory neurotransmission by serotonin in C. elegans. 2044 79


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