Muscarinic receptors depression

There is also evidence that the density of muscarinic receptors is increased in limbic regions of depressed patients who have committed suicide. If it is assumed that such a change reflects an increased activity of the cholinergic system, it could help to explain the reduced noradrenergic function as there is both clinical and experimental evidence to suggest that increased central cholinergic activity can precipitate depression and reduce noradrenergic activity. 

Evidence that central muscarinic receptors are supersensitive in depressed patients and that chronic antidepressant treatments normalize the supersensitivity of these receptors. This effect does not depend on any intrinsic anticholinergic activity of the antidepressant (i.e. it is an indirect, adaptive effect). 

The central cholinergic system has been implicated in the pathogenesis of affective disorder and in memory function, which is frequently found to be malfunctioning in depressed patients. The memory deficit elicited by chronic ECT in both patients and animals may be related to the decreased density and function of central muscarinic receptors, but it should be emphasized that the changes reported in cholinergic function are small and their relevance to the clinical situation remains to be established. 

The TCA drugs have lost their place as first-line therapy for depression because of their bothersome side effects (Table 33.2) at therapeutic doses and lethal effects in toxic doses. In addition to their presynaptic effects on the neuronal uptake of norepinephrine and serotonin, they block several postsynaptic receptors. They are potent cholinergic muscarinic receptor antagonists, resulting in symptoms such as dry mouth, constipation, tachycardia, blurred vision and urinary retention. Blockade of histamine receptors (Hi) often results in sedation and weight gain. Antagonism of aj-adrenoceptors in the vasculature can cause orthostatic hypotension. 

Mechanism of Action Anticholinergic alkaloids that inhibit the action of acetylcholine at postganglionic (muscarinic) receptor sites. Morphine (10% of opium) depresses cerebral cortex, hypothalamus, and medullary centers. Therapeutic Effect Decreases digestive secretions, increases GI muscle tone, reduces G1 force, alters pain perception and emotional response to pain. 

Levine J, Barak Y, Gonsalves M, et al A double-blind controlled trial of inositol treatment of depression. Am J Psychiatry 152 792-794, 1995a Levine J, Pomerantz T, Stier S, et al Lack of effect of 6 g inositol treatment on post-ECT cognitive function in humans. J Psychiatr Res 29 487-489, 1995b Levy A, Zohar J, Belmaker RH The effect of chronic lithium pretreatment on rat brain muscarinic receptor regulation. Neuropharmacology 21 1199-1201, 1983 Levy AB, Dixon KN, Schmidt H Sleep architecture in anorexia nervosa and bulimia. Biol Psychiatry 23 99-101, 1988... 

Results obtained from studies in gene-targeted mice indicate that ligands which selectively activate or inhibit single muscarinic receptor subtypes may be beneficial for the treatment of a number of diseases including, e.g., Alzheimer s and Parkinson s disease, depression, schizophrenia, and epilepsy. 

Zavitsanou K, Katsifis A, Mattner F, Huang XF. 2004b. Investigation of ml/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Neuropsychopharmacology 29 619-625. 

Sweating is stimulated by direct action of the increased endogenous acetylcholine on muscarinic receptors of sweat glands in the skin these glands are innervated by the sympathetic division of the autonomic nervous system. Agitation is produced by a central excitatory effect on cholinergic neurones in the brain, but in large doses anticholinesterases can cause depression of the respiratory centre in the medulla. 

Q9 The cholinergic effect of the anticholinesterase, operating via muscarinic receptors, causes intense bronchoconstriction and a considerable increase in fluid secretion into the bronchial lumen. This would cause Jim some obstructive problems with his breathing. If exposure to the malathion was prolonged, the respiratory centre in the medulla is likely to be depressed, so that support to his breathing would be required for a time, until the effects of the chemical had diminished. Assisted ventilation, frequent removal of bronchial secretions and oxygen are likely to be required. 

Atropine is used widely as an antispusmodic because nf its marked dcprcs.sant effect un parasympathctically innervated smooth mu.scle. It appetmt to block all muscarinic receptor subtypes. Atropine i.s. however, the standard by which other similar drugs are measured. Also, atropine has a blocking action on the transmi.ssion of the nerve impulse, rather than a depressant effect directly nn the mu.sculature. This action is termed neuroirnitic, in contrast with the action of an anti-spasmodic such us papaverine, which appears to act by depression uf tiic muscle cells and is termed musculolropic. 

IMS in OP-poisoned patients appears 24-96 h after an apparently well-treated acute cholinergic crisis phase. By definition, OP-poisoned patients should completely recover from the cholinergic crisis and then develop a syndrome. Clinically, IMS is characterized by acute paralysis and weakness in the territories of several cranial motor nerves, neck flexors, facial, extraocular, palatal, nuchal, proximal limb, and respiratory muscles 24-96 h after poisoning. Generalized weakness, depressed deep tendon reflexes, ptosis (drooping of the upper eyelids due to paralysis of the third cranial nerve), and diplopia (double vision of an object) are also evident. These symptoms may last for several days or weeks depending on the OP involved. Despite severe AChE inhibition, muscle fasciculations and muscarinic receptor-associated hypersecretory activities are absent. 

Excess synaptic acetylcholine stimulates muscarinic receptors (peripheral and CNS) and stimulates but then depresses or paralyzes nicotinic receptors." Activation of peripheral muscarinic receptors causes signs and symptoms described by the mnemonics SLUDGE or DUMB BELS, defined earlier. 

Cholinergic Actions in MOB Only limited information is available about cholinergic actions in MOB. Electrical activation of NDB has been reported to depress (Nickell and Shipley, 1988a) or increase (Kunze et al., 1991, 1992) mitral cell activity indirectly via primary effects on GABAergic GCs. NDB stimulation also reduced the field potential in the MOB caused by stimulation of the anterior commissure (Nickell and Shipley, 1993), an effect mediated by presynaptic inhibition of anterior commissure terminals via muscarinic receptors. One interpretation of these results is that cholinergic input to MOB may function to modulate interhemispheric transmission of olfactory information. In this regard, it is noteworthy that anterior commissural fibers are required for access and recall of olfactory memories between the two hemispheres. Infusion of ACh into MOB was reported to reduce paired-pulse depression of lateral olfactory tract (LOT)-evoked field potentials recorded in the GCL. This effect was attributed to... 

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