Failure of glycine site NMDA receptor antagonists to protect againstl-2-chloropropionic acid-induced neurotoxicity highlights the uniqueness of cerebellar NMDA receptors

1996 ◽  
Vol 738 (2) ◽  
pp. 236-242 ◽  
Author(s):  
P.S. Widdowson ◽  
A.J. Gyte ◽  
R. Upton ◽  
I. Wyatt
2019 ◽  
Vol 7 (4) ◽  
pp. 190-199
Author(s):  
A. P. Pereverzev ◽  
O. D. Ostroumova ◽  
O. N. Tkacheva ◽  
Y. V. Kotovskaya

For the treatment of dementia and Alzheimer’s disease, acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or the non-competitive inhibitor of N-methyl-D-aspartate receptors (NMDA receptors) memantine are currently used. The administration of these drugs can help temporarily improve or stabilize memory impairments and other cognitive functions, regress behavioral disorders, reduce the patient’s dependence on others, but at the same time can lead to the development of adverse drug reactions. The aim of this study was to analyze the information on the safety of acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the non-competitive inhibitor of NMDA receptors used to treat dementia. It was shown that stimulation of cholinergic receptors can lead to adverse drug reactions as contraction and narrowing of the pupil (miosis), an increase in lens curvature, accommodation spasm (visual impairment and an increased risk of falls), a decrease in heart rate (bradycardia) and inhibition of conduction of impulses through the conducting system heart, increased tone of the bronchi, gastrointestinal tract, gall and bladder, decreased tone of the sphincters of the digestive tract and bladder, increased secretion of exocrine and glands of the stomach, agitation, confusion. Blockade of NMDA receptors due to impairment of glutamate metabolism in the central nervous system may be the cause of neurotoxicity of NMDA receptor antagonists, and also causes dizziness, feeling of tiredness, hallucinations, drowsiness, and confusion. In case of development of adverse reactions, if possible, it is necessary to stop using the drug or reduce its dose, in case of an overdose or other need, prescribe symptomatic therapy. Information on the safety of cholinesterase inhibitors and NMDA receptor antagonists presented in the article is of practical importance for healthcare professionals, as it allows them to assess the possible risks associated with the use of drugs of these groups more accurately. In addition, the information can be used to optimize and individualize the pharmacotherapy regimens for patients with dementia, including the development of domestic protocols for the deprescribing of drugs (evidence-based practice of withdrawal, replacement or gradual dose reduction) in the elderly. 


ChemInform ◽  
2010 ◽  
Vol 29 (7) ◽  
pp. no-no
Author(s):  
R. H. KIM ◽  
J. I. CHOI ◽  
S. W. CHOI ◽  
K. S. LEE ◽  
Y. S. JUNG ◽  
...  

ChemInform ◽  
2010 ◽  
Vol 29 (24) ◽  
pp. no-no
Author(s):  
P. ACKLIN ◽  
H. ALLGEIER ◽  
Y. P. AUBERSON ◽  
S. BISCHOFF ◽  
S. OFNER ◽  
...  

ChemInform ◽  
2010 ◽  
Vol 22 (45) ◽  
pp. no-no
Author(s):  
P. D. LEESON ◽  
R. W. CARLING ◽  
J. D. SMITH ◽  
R. BAKER ◽  
A. C. FOSTER ◽  
...  

2003 ◽  
Vol 90 (4) ◽  
pp. 2098-2105 ◽  
Author(s):  
Brian E. Cairns ◽  
Peter Svensson ◽  
Kelun Wang ◽  
Steen Hupfeld ◽  
Thomas Graven-Nielsen ◽  
...  

Peripheral N-methyl-d-aspartate (NMDA) receptors are found in deep tissues and may play a role in deep tissue pain. Injection of the endogenous NMDA receptor agonist glutamate into the masseter muscle excites deep craniofacial afferent fibers in rats and evokes pain in human subjects. It is not clear whether peripheral NMDA receptors play a role in these effects of glutamate. Accordingly, the effect of NMDA on afferent activity as well as the effect of locally administered NMDA receptor antagonists on glutamate-evoked afferent discharges in acutely anesthetized rats and muscle pain in human subjects was examined. Injection of NMDA into the masseter muscle evoked afferent discharges in a concentration-related manner. It was found that the NMDA receptor antagonists 2-amino-5-phosphonvalerate (APV, 10 mM), ketamine (10 mM), and dextromethorphan (40 mM) significantly decreased glutamate-evoked afferent discharges. The effects of APV and ketamine, but not dextromethorphan, were selective for glutamate-evoked afferent discharges and did not affect hypertonic saline-evoked afferent discharges. In human experiments, it was found that 10 mM ketamine decreased glutamate-evoked muscle pain but had no effect on hypertonic saline-evoked muscle pain. These results indicate that injection of glutamate into the masseter muscle evokes afferent discharges in rats and muscle pain in humans in part through activation of peripheral NMDA receptors. It is conceivable that activation of peripheral NMDA receptors may contribute to masticatory muscle pain and that peripherally acting NMDA receptor antagonists could prove to be effective analgesics for this type of pain.


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