Introduction to neurobehavioral toxicology
Stanley Berent, James W. Albers in Neurobehavioral Toxicology, 2012
The cholinergic system, of course, is much more complex than described here. For instance, ACh may serve multiple roles in the nervous system, as a hormone or modulator of neurotransmission in addition to the more strict role of neurotransmission (Cooper et al., 1996). There are also multiple types of cholinergic receptor, the two primary classes being muscarinic and nicotinic, each further divided into subclasses. Likewise, there are multiple cholinesterases, with differing susceptibility to chemical inhibitors. The various receptor sites of the cholinergic system are often found in discrete anatomical locations, with direct implications for physiological functions mediated by these areas. For instance, the ACh stimulation in sweat glands can lead to diaphoresis, while blockade may produce anhidrosis. Muscarinic and nicotinic receptors are found in both the PNS and CNS, and both are widespread in the CNS (Siegel et al., 1999).
Biomarkers of Chemical Warfare Agents
Anthony P. DeCaprio in Toxicologic Biomarkers, 2006
The predominant nerve agents of historical note are the “G-agents” (GA-tabun, GB-sarin, GD-soman, GF-cyclo-sarin) and the “V-agents” (VX and, more recently, VR). Many of these nerve agents are related to common pesticides and function through inhibition of the enzyme acetylcholinesterase (AChE). AChE is a critical regulatory enzyme in the conduction of neuromuscular activity in that it breaks down the neurotransmitter acetylcholine (ACh). When the nerve agent binds to the active site of AChE, the enzyme can no longer function in destroying ACh. As ACh builds up in the neuromuscular junction, it causes continual nerve impulse generation and organ stimulation. Organs with cholinergic receptors include smooth muscle, skeletal muscle, central nervous system, and exocrine glands. The effects of nerve agent exposure vary based on dose and route of exposure but can range from miosis through increased secretions, bronchoconstriction, muscle fasciculations, to convulsions, seizures, loss of consciousness, and death at the higher exposures.
Iatrogenic psychosis
Anne M. Hassett, David Ames, Edmond Chiu in Psychosis in the Elderly, 2005
Alterations in neurotransmitter concentrations and the number of their associated receptor subtypes vary according to brain region (Sheldon, 1963). Furthermore, although the number of receptors may change there can be compensatory changes in their sensitivity. Reduced activity of the enzyme choline acetyl transferase, responsible for the production of acetylcholine and the associated changes in cholinergic receptors, is believed to be responsible for memory difficulties with aging (Bartus et al, 1982). In particular changes in cholinergic receptors in the hippocampus are believed to be pivotal in the memory difficulties associated with Alzheimer's disease. Changes in other neurotransmitter systems, particularly serotonin and noradrenaline, may contribute to the etiology of depression in the elderly (Salzman, 1984).
Tacrine and its 7-methoxy derivate; time-change concentration in plasma and brain tissue and basic toxicological profile in rats
Published in Drug and Chemical Toxicology, 2021
Jana Zdarova Karasova, Ondrej Soukup, Jan Korabecny, Milos Hroch, Marketa Krejciova, Martina Hrabinova, Jan Misik, Ladislav Novotny, Vendula Hepnarova, Kamil Kuca
The pharmacodynamics effects of these compounds are not based only on inhibitory action. Their pharmacological effect obviously involves several different pathways. Interaction with cholinergic receptors is a substantial part of the mechanism of action (Adem 1992, Soukup et al. 2011). M1 agonist can modify AD pathology at various levels and may bring long-term therapeutics effects in AD treatment (Fisher et al. 2000, Sepsova et al. 2015). However, the real tacrine mechanism of interaction with muscarinic receptors is still unknown. Its action is probably related to unselective muscarinic antagonism or M1 agonism with parallel M2 antagonism. The muscarinic antagonism on M2 muscarinic receptor leads to an increased releasing of acetylcholine in brain tissue (Fisher et al. 2000, Rusted et al. 2000). This kind of muscarinic interaction provides a promising therapeutic potency in AD treatment. Tacrine derivate 7-MEOTA shows higher affinity to muscarinic receptors than tacrine. From this point of view 7-MEOTA may be considered as more promising compound (Sepsova et al. 2015).
Nicotine intoxication by e-cigarette liquids: a study of case reports and pathophysiology
Published in Clinical Toxicology, 2020
Gerdinique C. Maessen, Anjali M. Wijnhoven, Rosalie L. Neijzen, Michelle C. Paulus, Dayna A. M. van Heel, Bart H. A. Bomers, Lucie E. Boersma, Burak Konya, Marcel A. G. van der Heyden
The described seizures and myoclonus have two possible explanations, depending on a physician’s definition of these terms. First, nicotinic cholinergic receptors are, besides paravertebrally, situated at the neuromuscular junction. Nicotine acts as a substitute for acetylcholine and as such stimulates more rapid depolarisation of the muscle fibres. In high concentrations, it can induce involuntary contraction of the muscles, even resulting in seizure-like movements [47]. Second, at very high dosage, nicotine can cause epileptic activity in the brain. This mechanism is not yet fully understood, but may be related to desensitisation of the cholinergic receptors after prolonged exposure. The cholinergic receptors in the central nervous system normally stimulate GABAergic interneurons, which in turn have an inhibitory effect on the pyramidal cells. A decrease in cholinergic receptors reduces the GABAergic activity and has an excitatory effect on the pyramidal cells, resulting in seizure [48,49]. The desensitisation of the nicotinic cholinergic receptors eventually induces a similar effect at the neuromuscular junction. Lengthened exposure to nicotine leads to a reduction in available receptors at the muscle cell membrane, followed by decreased cell depolarisation. In this way, partial or complete muscle paralysis may occur [16].
Anticholinergic medications and risk of dementia in older adults: Where are we now?
Published in Expert Opinion on Drug Safety, 2020
Satabdi Chatterjee, Ashna Talwar, Rajender R. Aparasu
The cognitive adverse effects of anticholinergics have received increased attention due to efforts in identifying risk factors that can be targeted to delay the risk of dementia and the limited benefits of pharmacotherapy in dementia. Available evidence primarily from animal models appears to suggest that the anticholinergic medications nonselectively block the cholinergic receptors, which tend to increase beta-amyloid plaques and neurofibrillary tau proteins, and lead to severe dementia [52]. Cholinergic transmission plays a crucial role in various cognitive processes, such as learning, memory, attention, and organization [53]. Consequently, blocking the cholinergic neurotransmission has been associated with cell death and memory deficits that are typically present in severe dementia cases [52].
Related Knowledge Centers
- Integral Membrane Protein
- Metabotropic Receptor
- Nicotine
- Nicotinic Acetylcholine Receptor
- Neurotransmitter
- Cell Surface Receptor
- Ion Channel
- Acetylcholine
- Ligand-Gated Ion Channel
- Muscarinic Acetylcholine Receptor