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Cholinergic Receptors (cholinergic + receptor)
Selected AbstractsThe undesirable effects of neuromuscular blocking drugsANAESTHESIA, Issue 2009C. Claudius Summary Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking drugs including the definitions, diagnosis and causes of hypersensitivity reactions and postoperative residual curarisation. [source] More types than one: multiple muscarinic receptor coupled K+ currents undergo remodelling in an experimental model of atrial fibrillationBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2007A F James The common cardiac arrhythmia atrial fibrillation (AF) tends to show progression in its severity, which is associated with ,remodelling': structural and electrophysiological changes that facilitate arrhythmia induction and maintenance. In this issue of the BJP, Yeh and colleagues demonstrate for the first time, down-regulation of three types of muscarinic cholinergic receptor (mAChR) coupled K+ currents (IKM2, IKM3 and IKM4) and of M2, M3 and M4 mAChR subtype proteins, in a canine model of atrial tachycardia (AT) induced remodelling. The IKMs and their extent of AT-induced remodelling were similar in left-atrial and pulmonary vein (PV) myocytes, so remodelling of M2,M4 receptor-linked currents appears not to underlie the unique contribution of PVs to AF. Parasympathetic stimulation can increase susceptibility to AF; thus remodelling of M2,M4 receptors and K+ currents could be adaptive in AT. Further work is warranted to determine whether or not remodelling of multiple mAChRs and currents also contributes to human AF. British Journal of Pharmacology (2007) 152, 981,983; doi:10.1038/sj.bjp.0707437; published online 10 September 2007 [source] Cholinergic modulation of visuospatial responding in central thalamusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2007Lori A. Newman Abstract Central thalamus has extensive connections with basal ganglia and frontal cortex that are thought to play a critical role in sensory-guided goal-directed behavior. Central thalamic activity is influenced by cholinergic projections from mesopontine nuclei. To elucidate this function we trained rats to respond to lights in a reaction time (RT) task and compared effects of muscarinic (2.4, 7.3, 22 nmol scopolamine) and nicotinic (5.4, 16, 49, 98 nmol mecamylamine) antagonists with the GABAA agonist muscimol (0.1, 0.3, 1.0 nmol) in central thalamus. We compared this with subcutaneous (systemic) effects of mecamylamine (3.2, 9.7, 29 µmol/kg) and scopolamine (0.03, 0.09, 0.26 µmol/kg). Subcutaneous scopolamine increased omissions (failure to respond within a 3-s response window) at the highest dose tested. Subcutaneous mecamylamine increased omissions at the highest dose tested while impairing RT and per cent correct at lower doses. Intrathalamic injections of muscimol and mecamylamine decreased per cent correct at doses that did not affect omissions or RT. Intrathalamic scopolamine increased omissions and RT at doses that had little effect on per cent correct. Anatomical controls indicated that the effects of mecamylamine were localized in central thalamus and those of scopolamine were not. Drug effects did not interact with attention-demanding manipulations of stimulus duration, proximity of stimulus and response locations, or stimulus array size. These results are consistent with the hypothesis that central thalamus mediates decisional processes linking sensory stimuli with actions, downstream from systems that detect sensory signals. They also provide evidence that this function is specifically influenced by nicotinic cholinergic receptors. [source] Muscarinic receptor blockade in ventral hippocampus and prelimbic cortex impairs memory for socially transmitted food preferenceHIPPOCAMPUS, Issue 5 2009Anna Carballo-Márquez Abstract Acetylcholine is involved in learning and memory and, particularly, in olfactory tasks, but reports on its specific role in consolidation processes are somewhat controversial. The present experiment sought to determine the effects of blocking muscarinic cholinergic receptors in the ventral hippocampus (vHPC) and the prelimbic cortex (PLC) on the consolidation of social transmission of food preference, an odor-guided relational task that depends on such brain areas. Adult male Wistar rats were bilaterally infused with scopolamine (20 ,g/site) immediately after social training and showed impairment, relative to vehicle-injected controls, in the expression of the task measured 24 h after learning. Results indicated that scopolamine in the PLC completely abolished memory, suggesting that muscarinic transmission in this cortical region is crucial for consolidation of recent socially acquired information. Muscarinic receptors in the vHPC contribute in some way to task consolidation, as the rats injected with scopolamine in the vHPC showed significantly lower trained food preference than control rats, but higher than both chance level and that of the PLC-injected rats. Behavioral measures such as social interaction, motivation to eat, neophobia, or exploration did not differ between rats infused with scopolamine or vehicle. Such data suggest a possible differential role of muscarinic receptors in the PLC and the vHPC in the initial consolidation of a naturalistic form of nonspatial relational memory. © 2008 Wiley-Liss, Inc. [source] Post-operative pain relief following intrathecal injection of acetylcholine esterase inhibitor during lumbar disc surgery: a prospective double blind randomized studyJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2008Z. H. Khan MD Summary Background:, As spinal cholinergic receptors participate in the control of somatic pain, this effect could be potentiated by intrathecal injection of a cholinesterase inhibitor, neostigmine. Objective:, This study was designed to evaluate the effectiveness of intrathecal administration of neostigmine on pain relief after single level lumbar disectomy. Methods:, Sixty-six patients with unilateral extruded lumbar disc were randomly allocated into two groups, neostigmine (,N'), and control (,C'); the former received 100 ,g of neostigmine methylsulphate, whereas the latter received placebo intrathecally after termination of the surgery. Visual Analogue Scale was employed to measure post-operative pain, which was a primary outcome of the study. Opiate dosage consumed was also recorded as a primary outcome during the first 24 h following surgery. Nausea and vomiting although important were considered as secondary outcomes. Results:, Mean Visual Analogue Scale scores post-operatively at 1, 4 and 8 h were 2·24, 1·82 and 1·88 in group ,N' and 5·36, 5·61 and 4·88 in group C. Mean morphine used intravenously in the first 24 h was 0·9 mg in group ,N' and 4·7 mg in group C. All results were found to be significantly different in the two groups. The frequency of nausea and vomiting was not significantly different in the two groups ,C' (24%) and ,N' (18%). Conclusion:, Injection of 100 ,g hyperbaric neostigmine intrathecally was effective for pain relief, and reduced post-operative opiate demand. [source] Anthelmintic paraherquamides are cholinergic antagonists in gastrointestinal nematodes and mammalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2002Erich W. Zinser Oxindole alkaloids in the paraherquamide/marcfortine family exhibit broad-spectrum anthelmintic activity that includes drug-resistant strains of nematodes. Paraherquamide (PHQ), 2-deoxoparaherquamide (2DPHQ), and close structural analogs of these compounds rapidly induce flaccid paralysis in parasitic nematodes in vitro, without affecting adenosine triphosphate (ATP) levels. The mechanism of action of this anthelmintic class was investigated using muscle tension and microelectrode recording techniques in isolated body wall segments of Ascaris suum. None of the compounds altered A. suum muscle tension or membrane potential. However, PHQ blocked (when applied before) or reversed (when applied after) depolarizing contractions induced by acetylcholine (ACh) and the nicotinic agonists levamisole and morantel. These effects were mimicked by the nicotinic ganglionic blocker mecamylamine, suggesting that the anthelmintic activity of PHQ and marcfortines is due to blockade of cholinergic neuromuscular transmission. The effects of these compounds were also examined on subtypes of human nicotinic ACh receptors expressed in mammalian cells with a Ca2+ flux assay. 2DPHQ blocked nicotinic stimulation of cells expressing ,3 ganglionic (IC50 , 9 µm) and muscle-type (IC50 , 3 µm) nicotinic cholinergic receptors, but was inactive at 100 µm vs. the ,7 CNS subtype. PHQ anthelmintics are nicotinic cholinergic antagonists in both nematodes and mammals, and this mechanism appears to underlie both their efficacy and toxicity. [source] Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn.PHYTOTHERAPY RESEARCH, Issue 3 2002Vikas Kumar Abstract The high affinity binding sites for serotonin and benzodiazepine in the frontal cortex, for dopamine in the striatum and muscarinic cholinergic receptors in the hippocampus were investigated in the brains of Charles Foster rats treated for 3 days. Transfer latency on elevated plus maze (TL), passive and active avoidance behaviour (PA and AA) and electroconvulsive shock (ECS) induced amnesia were also studied. Pilot studies indicated that single dose administration of Indian Hypericum perforatum (IHp) had little or no acute behavioural effects and hence the extract of IHp was administered orally at two dose levels (100 and 200,mg/kg, p.o.) once daily for 3 consecutive days, while piracetam (500,mg/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard nootropic agent. Control rats were treated with an equal volume of vehicle (0.3%,carboxymethyl cellulose). The results indicate that IHp treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and an increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Preliminary pharmacological studies with IHp extract indicate the presence of two major behavioural actions, namely, antidepressant and anxiolytic. The present findings tend to elucidate the mechanism of earlier observations, the downregulation of the dopamine D2 receptor being consonant with anxiolytic and the upregulation of 5-HT2A and BDZ receptors being consonant with antidepressant activity. Piracetam when given alone, shortened the TL on days 1, 2 and 9 day and also antagonized the amnesic effects of ECS on the TL significantly, whereas IHp antagonized the amnesia produced by ECS. IHp had no significant effect per se on the retention of the PA in rats but produced a significant reversal of ECS induced PA retention deficit. Piracetam showed a significant facilitatory effect per se on PA retention and also reversed the ECS induced impaired PA retention. In the AA test, piracetam facilitated the acquisition and retention of AA in rats but IHp had no effect per se. Both the doses of IHp and piracetam significantly attenuated the ECS induced impaired retention of AA. These results indicate a possible nootropic action of IHp in amnesic animals, which was comparable qualitatively to piracetam. Copyright © 2002 John Wiley & Sons, Ltd. [source] Annotation: The role of prefrontal deficits, low autonomic arousal, and early health factors in the development of antisocial and aggressive behavior in childrenTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 4 2002Adrian Raine Background: This article selectively reviews the biological bases of antisocial and aggressive behavior in children with a focus on low autonomic functioning, prefrontal deficits, and early health factors. Results: Low resting heart rate is thought to be the best-replicated biological correlate of antisocial and aggressive behavior in child and adolescent populations and may reflect reduced noradrenergic functioning and a fearless, stimulation-seeking temperament. Evidence from neuropsychological, neurological, and brain imaging studies converges on the conclusion that prefrontal structural and functional deficits are related to antisocial, aggressive behavior throughout the lifespan. A prefrontal dysfunction theory of antisocial behavior is advanced. This argues that social and executive function demands of late adolescence overload the late developing prefrontal cortex, giving rise to prefrontal dysfunction and a lack of inhibitory control over antisocial, violent behavior that peaks at this age. Birth complications and minor physical anomalies are selectively associated with later violent behavior, especially when combined with adverse psychosocial risk factors for violence. Cigarette smoking during pregnancy may increase the risk for antisocial and violent behavior in later life by disrupting noradrenergic functioning and enhancement of cholinergic receptors that inhibit cardiac functioning. Malnutrition during pregnancy is associated with later antisocial behavior and may be mediated by protein deficiency. Conclusions: It is argued that early health intervention and prevention studies may provide the most effective way of reversing biological deficits that predispose to antisocial and aggressive behavior in children and adults. [source] The Effects of the ,2 -Adrenergic Receptor Agonists Clonidine and Rilmenidine, and Antagonists Yohimbine and Efaroxan, on the Spinal Cholinergic Receptor System in the RatBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2004Klas S. P. Abelson The cholinergic receptor system interacts with several other receptor types, such as ,2 -adrenergic receptors. To fully understand these interactions, the effects of various receptor ligands on the cholinergic system must be investigated in detail. This study was initiated to investigate the effects of the ,2 -adrenergic receptor agonists clonidine and rilmenidine and the ,2 -adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors in the rat. Spinal microdialysis was used to measure in vivo changes of acetylcholine after administration of the ligands, with or without nicotinic receptor blockade. In addition, in vitro binding properties of the ligands on muscarinic and nicotinic receptors were investigated. It was found that clonidine and rilmenidine increased, while yohimbine decreased spinal acetylcholine release. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade attenuated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand, all ligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curve and rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested ,2 -adrenergic receptor ligands affect intraspinal acetylcholine release in the rat evoked by nicotinic receptor mechanisms in vivo, and that they possess binding affinity to nicotinic receptors in vitro. The binding of ,2 -adrenergic receptor ligands to nicotinic receptors might affect the intraspinal release of acetylcholine. [source] | |||||||||||||