Cholinergic agents. Medical search

Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.

Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of ACETYLCHOLINE, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of MUSCARINIC AGONISTS, although most modern texts discourage that usage.

A superfamily of nematodes of the order STRONGYLIDA. Characteristics include a fluid-filled outer layer of cuticle and a reduced mouth and bursa.

A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.

A genus of parasitic nematodes of the superfamily METASTRONGYLOIDEA. Two species, ANGIOSTRONGYLUS CANTONENSIS and A. vasorum, infest the lungs of rats and dogs, respectively. A. cantonensis is transmissible to man where it causes frequently fatal infection of the central nervous system.

A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.

An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.

Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.

Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.

Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.

One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.

A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.

Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.

One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.

DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model. (1/352)

Myotonic dystrophy (DM) is the most common form of muscular dystrophy and is caused by expansion of a CTG trinucleotide repeat on human chromosome 19. Patients with DM develop atrioventricular conduction disturbances, the principal cardiac manifestation of this disease. The etiology of the pathophysiological changes observed in DM has yet to be resolved. Haploinsufficiency of myotonic dystrophy protein kinase (DMPK), DM locus-associated homeodomain protein (DMAHP) and/or titration of RNA-binding proteins by expanded CUG sequences have been hypothesized to underlie the multi-system defects observed in DM. Using an in vivo murine electrophysiology study, we show that cardiac conduction is exquisitely sensitive to DMPK gene dosage. DMPK-/- mice develop cardiac conduction defects which include first-, second-, and third-degree atrioventricular (A-V) block. Our results demonstrate that the A-V node and the His-Purkinje regions of the conduction system are specifically compromised by DMPK loss. Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients. These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy. (+info)

Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick alpha7 nicotinic receptor. (2/352)

1. We assessed the pharmacological activity of triethyl-(beta-4-stilbenoxy-ethyl) ammonium (MG624), a drug that is active on neuronal nicotinic receptors (nicotinic AChR). Experiments on the major nicotinic AChR subtypes present in chick brain, showed that it inhibits the binding of [125I]-alphaBungarotoxin (alphaBgtx) to the alpha7 subtype, and that of [3H]-epibatidine (Epi) to the alpha4beta2 subtype, with Ki values of respectively 106 nM and 84 microM. 2. MG624 also inhibited ACh elicited currents (I(ACh)) in the oocyte-expressed alpha7 and alpha4beta2 chick subtypes with half-inhibitory concentrations (IC50) of respectively 109 nM and 3.2 microM. 3. When tested on muscle-type AChR, it inhibited [125I]-alphaBgtx binding with a Ki of 32 microM and ACh elicited currents (I(ACh)) in the oocyte-expressed alpha1beta1gammadelta chick subtype with an IC50 of 2.9 microM. 4. The interaction of MG624 with the alpha7 subtype was investigated using an alpha7 homomeric mutant receptor with a threonine-for-leucine 247 substitution (L247T alpha7). MG624 did not induce any current in oocytes expressing the wild type alpha7 receptor, but did induce large currents in the oocyte-expressed L247T alpha7 receptor. The MG624 elicited current (I(MG62)) has an EC50 of 0.2 nM and a Hill coefficient nH of 1.9, and is blocked by the nicotinic receptor antagonist methyllycaconitine (MLA). 5. These binding and electrophysiological studies show that MG624 is a potent antagonist of neuronal chick alpha7 nicotinic AChR, and becomes a competitive agonist following the mutation of the highly conserved leucine residue 247 located in the M2 channel domain. (+info)

Cholinomimetic action of macrolide antibiotics on airway gland electrolyte secretion. (3/352)

We investigated the acute effects of erythromycin (EM) and its derivatives on ionic currents in airway glands from feline tracheae. Therapeutic concentrations of EM or clarithromycin (CAM) attenuated the whole cell currents evoked by ACh in a competitive manner. The maximally stimulated inward Cl- currents were reduced to 54 and 83% and the outward K+ currents to 55 and 84% of control values by EM and CAM, respectively, whereas the responses induced by phenylephrine, norepinephrine, caffeine, or ionomycin were unaffected by EM, CAM, or EM523, a synthetic derivative of EM. K+ channels in excised outside-out patches were not influenced by macrolides. Although therapeutic concentrations of macrolides showed no effect on the baseline currents, high concentrations of macrolides alone evoked currents mimicking the ACh response, which were abolished completely by atropine. We concluded that macrolides act as a partial agonist on cholinergic receptors, resulting in a reduction of Cl- secretion at pharmacological doses of the agents, which may exhibit a pronounced effectiveness on hypertrophied and/or cholinergically sensitized submucosal glands in pathological airways. (+info)

Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin. (4/352)

Changes in brain electrical activity in response to cholinergic agonists, antagonists, or excitotoxic lesions of the basal forebrain may not be reflective entirely of changes in cholinergic tone, in so far as these interventions also involve noncholinergic neurons. We examined electrocortical activity in rats following bilateral intracerebroventricular administration of 192 IgG-saporin (1.8 microg/ventricle), a selective cholinergic immunotoxin directed to the low-affinity nerve growth factor receptor p75. The immunotoxin resulted in extensive loss of choline acetyl transferase (ChAT) activity in neocortex (80%-84%) and hippocampus (93%), with relative sparing of entorhinal-piriform cortex (42%) and amygdala (28%). Electrocortical activity demonstrated modest increases in 1- to 4-Hz power, decreases in 20- to 44-Hz power, and decreases in 4- to 8-Hz intra- and interhemispheric coherence. Rhythmic slow activity (RSA) occurred robustly in toxin-treated animals during voluntary movement and in response to physostigmine, with no significant differences seen in power and peak frequency in comparison with controls. Physostigmine significantly increased intrahemispheric coherence in lesioned and intact animals, with minor increases seen in interhemispheric coherence. Our study suggests that: (1) electrocortical changes in response to selective cholinergic deafferentation are more modest than those previously reported following excitotoxic lesions; (2) changes in cholinergic tone affect primarily brain electrical transmission within, in contrast to between hemispheres; and (3) a substantial cholinergic reserve remains following administration of 192 IgG-saporin, despite dramatic losses of ChAT in cortex and hippocampus. Persistence of a cholinergically modulated RSA suggests that such activity may be mediated through cholinergic neurons which, because they lack the p75 receptor, remain unaffected by the immunotoxin. (+info)

Minor structural changes in nicotinoid insecticides confer differential subtype selectivity for mammalian nicotinic acetylcholine receptors. (5/352)

The major nitroimine insecticide imidacloprid (IMI) and the nicotinic analgesics epibatidine and ABT-594 contain the 6-chloro-3-pyridinyl moiety important for high activity and/or selectivity. ABT-594 has considerable nicotinic acetylcholine receptor (AChR) subtype specificity which might carry over to the chloropyridinyl insecticides. This study considers nine IMI analogues for selectivity in binding to immuno-isolated alpha1, alpha3 and alpha7 containing nicotinic AChRs and to purported alpha4beta2 nicotinic AChRs. Alpha1- and alpha3-containing nicotinic AChRs (both immuno-isolated by mAb 35, from Torpedo and human neuroblastoma SH-SY5Y cells, respectively) are between two and four times more sensitive to DN-IMI than to (-)-nicotine. With immuno-isolated alpha3 nicotinic AChRs, the tetrahydropyrimidine analogues of IMI with imine or nitromethylene substituents are 3-4 fold less active than (-)-nicotine. The structure-activity profile with alpha3 nicotinic AChRs from binding assays is faithfully reproduced in agonist potency as induction of 86rubidium ion efflux in intact cells. Alpha7-containing nicotinic AChRs of SH-SY5Y cells (immuno-isolated by mAb 306) and rat brain membranes show maximum sensitivity to the tetrahydropyrimidine analogue of IMI with the nitromethylene substituent. The purported alpha4beta2 nicotinic AChRs [mouse (Chao & Casida, 1997) and rat brain] are similar in sensitivity to DN-IMI, the tetrahydropyrimidine nitromethylene and nicotine. The commercial insecticides (IMI, acetamiprid and nitenpyram) have low to moderate potency at the alpha3 and purported alpha4beta2 nicotinic AChRs and are essentially inactive at alpha1 and alpha7 nicotinic AChRs. In conclusion, the toxicity of the analogues and metabolites of nicotinoid insecticides in mammals may involve action at multiple receptor subtypes with selectivity conferred by minor structural changes. (+info)

Selective excitation of subtypes of neocortical interneurons by nicotinic receptors. (6/352)

The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbumin-expressing fast spiking interneurons and somatostatin-expressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-beta-erythroidine and mecamylamine and persisted in the presence of the alpha7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the alpha7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the alpha4, alpha5, and beta2 nicotinic receptor subunits. Therefore, these results provide a role for non-alpha7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine. (+info)

Perspectives of pharmacotherapy in Alzheimer's disease. (7/352)

Alzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans, and it is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. The senile plaques are composed of amyloid beta-peptides (A beta), 40-42 amino acid peptide fragments of the beta-amyloid precursor protein. Genetic, molecular biological and neuropharmacological evidence support the 'amyloid cascade hypothesis' for the pathogenesis of the disease. We review the in vivo effects of various compounds on behavioral and neuropathological changes in the non-transgenic animal models of AD produced by continuous i.c.v. infusion of A beta. These results support therapeutic strategies such as cholinergic therapy, anti-inflammatory agents, antioxidants and estrogen replacement therapy, as well as other cognition enhancers for the treatment of AD. In addition, the amyloid cascade hypothesis offers a number of potential targets for novel therapeutic strategies in AD. We believe that our non-transgenic animal model, as well as transgenic animal models, are useful for developing novel pharmacotherapeutics in AD. (+info)

Redundant basal forebrain modulation in taste aversion memory formation. (8/352)

Mnemonic deficits resulting from excitotoxic lesion of the basal forebrain have been classically attributed to the resulting depletion of cortical acetylcholine activity. It has been demonstrated that in spite of the strong cholinergic depletion after injections into the basal forebrain of the immunotoxin 192IgG-saporin, no detectable deficit can be found in the acquisition of several learning tasks, including conditioned taste aversion. Conversely, NMDA-induced lesions of the basal forebrain strongly impair taste aversion learning. In this study we show that 192IgG-saporin produces an efficient and selective cholinergic deafferentation of the rat neocortex but not the amygdala. Furthermore, a stronger relationship between severity of memory impairment after NMDA lesions and basoamygdaloid cholinergic deafferentation was found. Therefore, in a second experiment, we show that combining NMDA-induced lesions into the basolateral amygdala with 192IgG-saporin injections into the basal forebrain results in a strong disruption of taste aversion learning, whereas none of these treatments were by themselves capable of producing any detectable impairment in this learning task. The double lesion effect was only paralleled by simple NMDA lesions into the basal forebrain, suggesting that the learning deficits associated to excitotoxic lesions of the basal forebrain are the result of the simultaneous destruction of the corticopetal and basoamygdaloid interaction. A model is proposed, according to which the modulation of learning processes exerted by the basal forebrain can be redundantly performed by both the basocortical and basoamygdaloid pathway. (+info)

... agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" ... A receptor is cholinergic if it uses acetylcholine as its neurotransmitter. A synapse is cholinergic if it uses acetylcholine ... Thus it was proposed that degeneration of cholinergic neurons in the basal forebrain and the associated loss of cholinergic ... Adults with AD presenting with dysfunction of the cholinergic system are not able to compensate for long-term and working ...

https://en.wikipedia.org/wiki/Cholinergic

Ganglionic blocker Cholinergic blocking drugs "Dorlands Medical Dictionary:neuromuscular blocking agent".[permanent dead link] ... Depolarizing agents Depolarizing agents produce their block by binding to and activating the ACh receptor, at first causing ... Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber. This persistent ... These drugs fall into two groups: Non-depolarizing blocking agents: These agents constitute the majority of the clinically ...

https://en.wikipedia.org/wiki/Neuromuscular-blocking_drug