Tolerance to anticholinesterase compounds in mammals

Costa, Lucio G.; Schwab, Bradley W.; Murphy, Sheldon D.

doi:10.1016/0300-483x(82)90021-x

Cited by 133 publications

(28 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is well established that some ChEI elicit tolerance [6] . Previous results have shown that the response to certain agents, especially tacrine, diminishes considerably after a second injection.…”

Section: Discussionmentioning

confidence: 99%

Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats

Liang

Tang

2006

Acta Pharmacologica Sinica

View full text Add to dashboard Cite

Aim: To assess the effects of cholinesterase inhibitors huperzine A, donepezil and rivastigmine on cerebral neurotransmitters in the cortex and hippocampus in freely-moving rats. Methods: Double-probe cerebral microdialysis and HPLC with electrochemical detection were used to detect neurotransmitters. Results: Our results showed that huperzine A (0.25, 0.5, and 0.75 µmol/kg, po) dose-dependently elevated extracellular acetylcholine (ACh) levels in the medial prefrontal cortex (mPFC) and hippocampus. Oral administration of donepezil (5.4 µmol/kg) or rivastigmine (1 µmol/kg) also elicited significant increases in ACh in the mPFC and hippocampus. The time course of cortical acetylcholinesterase (AChE) inhibition with the 3 inhibitors mirrored the increases of ACh at the same dose. The marked elevation of ACh after oral administration of huperzine A (0.5 µmol/kg) and donepezil (5.4 µmol/kg) was associated with a significantly increased release of dopamine (DA) in the mPFC or hippocampus. None of the 3 inhibitors affected norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the mPFC and hippocampus. The effects of huperzine A and rivastigmine did not depend on the route of administration, but donepezil was less efficacious by the oral route than by ip injection. The ability of huperzine A to increase ACh levels was unchanged when tests were performed after multiple oral administration of the drug at 0.5 µmol/kg, once per day for 30 d. Conclusion: The present findings showed that, in molar terms, huperzine A had similar potency on increasing mPFC ACh and DA levels as compared to the 11-and 2-fold dosages of donepezil and rivastigmine, respectively, and had longer lasting effects after oral dosing.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats

Liang

Tang

2006

Acta Pharmacologica Sinica

View full text Add to dashboard Cite

show abstract

“…While compensatory downregulation of postsynaptic cholinergic receptors is considered a primary mechanism of tolerance to AChE inhibitors (Costa et al, 1982;Russell and Overstreet, 1987), compensatory presynaptic processes may also participate in the ultimate expression of toxicity with CPF. It has been reported that a subpopulation of muscarinic receptors selectively labeled by [ 3 H]c«-methyldioxolane (CD) is primarily of the m2-subtype (Huff and AbouDonia, 1994) and located mainly on presynaptic terminals (Watson et al, 1986).…”

Section: Society Of Toxkotofymentioning

confidence: 99%

Effects of Chlorpyrifos on High-Affinity Choline Uptake and [³H]Hemicholinium-3 Binding in Rat Brain

Liu

Pope

1996

Toxicol Sci

View full text Add to dashboard Cite

“…Many reports have indicated that some OP insecticides can interact with macromolecular targets in addition to AChE, including muscarinic receptors (Bakry et al, 1988;Jett et al, 1991;Ward et al, 1993, Huff et al, 1994Huff and Abou-Donia, 1995;Ward and Mundy, 1996;van den Beukel et al, 1997, Quistad et al, 2001, Quistad and Casida, 2004. It is well known that prolonged AChE inhibition leads to a reduction in cholinergic receptor density at innervated sites, contributing to the development of tolerance to cholinergic toxicity (Costa et al, 1982a). The toxicological consequences of direct binding of some OPs to cholinergic receptors remains unclear, however.…”

Section: Introductionmentioning

confidence: 99%

Comparative effects of oral chlorpyrifos exposure on cholinesterase activity and muscarinic receptor binding in neonatal and adult rat heart

et al. 2007

View full text Add to dashboard Cite

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M 2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M 2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor-mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M 2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD 10 : neonates, 7.5 and 15 mg/ kg; adults, 68 and 136 mg/kg). Dose-and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD 10 , relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC 50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not responsible for the age-related difference in cholinesterase sensitivity between age groups. Pre-incubation of neonatal and adult tissues with selective inhibitors of AChE and butyrylcholinesterase (BChE) indicated that a majority (82-90%) of ChE activity in the heart of both neonates and adults was BChE. The rapid onset (by 4 hours after dosing) of changes in muscarinic receptor binding in adult heart may be a reflection of the more potent direct binding to muscarinic receptors by chlorpyrifos oxon previously reported in adult tissues. The results suggest that ChE activity (primarily BChE) in neonatal heart may be inherently more sensitive to inhibition by some anticholinesterases and that toxicologically significant binding to muscarinic receptors may be

show abstract

Tolerance to anticholinesterase compounds in mammals

Cited by 133 publications

References 76 publications

Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats

Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats

Effects of Chlorpyrifos on High-Affinity Choline Uptake and [³H]Hemicholinium-3 Binding in Rat Brain

Comparative effects of oral chlorpyrifos exposure on cholinesterase activity and muscarinic receptor binding in neonatal and adult rat heart

Contact Info

Product

Resources

About

Tolerance to anticholinesterase compounds in mammals

Cited by 133 publications

References 76 publications

Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats

Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats

Effects of Chlorpyrifos on High-Affinity Choline Uptake and [3H]Hemicholinium-3 Binding in Rat Brain

Comparative effects of oral chlorpyrifos exposure on cholinesterase activity and muscarinic receptor binding in neonatal and adult rat heart

Contact Info

Product

Resources

About

Effects of Chlorpyrifos on High-Affinity Choline Uptake and [³H]Hemicholinium-3 Binding in Rat Brain