Neurons anesthetics

SK-N-SH Human neuroblastoma Neuron Anesthetic N20 Depressed cholinergic Ca2+ signaling... 

In anesthetized rats, amphetamine causes dose-dependent changes in neostriatal unit activity. Spontaneously aetive neostriatal cells are uniformly inhibited at low (<2.0 mg/kg, IP) doses. At intermediate doses, an initial exeitation precedes the inhibition, and, at high doses (>5.0 mg/kg, IP), the predominant effect is excitation (Groves and Rebec 1976). Regional differences in the direction, magnitude, and duration of the response of neurons in the neostriatum exist (Rebee and Curtis 1983). 

Warenycia, M.W., and McKenzie, G.M. Responses of striatal neurons to anesthetics and analgesics in freely moving rats. Gen Pharmacol 15 517-522, 1984b. 

The mechanism of action of these anesthetics involves the blockade of sodium channels in the membrane of the second-order sensory neuron. The binding site for these anesthetics is on a subunit of the sodium channel located near the internal surface of the cell membrane. Therefore, the agent must enter the neuron in order to block the sodium channel effectively. Without the influx of sodium, neurons cannot depolarize and generate an action potential, so the second-order sensory neuron cannot be stimulated by impulses elicited by pain receptors associated with the first-order sensory neuron. In other words, the pain signal is effectively interrupted at the level of the spinal cord and does not travel any higher in the CNS. In this way, the brain does not perceive pain. 

Most hypnotic drugs act on GABA receptors. It is reasonable to hypothesize that hypnotic actions are mediated by the GABA receptors on wake-promoting neurons innervated by POA sleep-active neurons, but there is little study of this problem. However, there is evidence that GABAergic anesthetics induce c-Fos IR in the VLPO and suppress c-Fos IR in histaminergic neurons (Nelson et al, 2002). 

Reiner, P. B., Semba, K., Fibiger, H. C. McGeer, E. G. (1987). Physiological evidence for subpopulations of cortically projecting basal forebrain neurons in the anesthetized rat. Neuroscience 20, 629-36. 

Bupivacaine influx, leading to neuronal membrane hyperpolarization Anesthetic, binds to sodium channel, decreases sodium... 

The clinical effects of chloroform toxicity on the central nervous system are well documented. However, the molecular mechanism of action is not well understood. It has been postulated that anesthetics induce their action at a cell-membrane level due to lipid solubility. The lipid-disordering effect of chloroform and other anesthetics on membrane lipids was increased by gangliosides (Harris and Groh 1985), which may explain why the outer leaflet of the lipid bilayer of neuronal membranes, which has a large ganglioside content, is unusually sensitive to anesthetic agents. Anesthetics may affect calcium-dependent potassium conductance in the central nervous system (Caldwell and Harris 1985). The blockage of potassium conductance by chloroform and other anesthetics resulted in depolarization of squid axon (Haydon et al. 1988). 

The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures (inert gas xenon hydrocarbons halogenated hydrocarbons) possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and lipophilicity of anesthetic drugs (A). However, an interaction with lipophilic domains of membrane proteins is also conceivable. Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic N2O must be inhaled in high concentrations (>70% of inspired air has to be replaced), much smaller concentrations (<5%) are required in the case of the more lipophilic halothane. 

Substances from different chemical classes suspend consciousness when given intravenously and can be used as injectable anesthetics (B). Unlike inha-lational agents, most of these drugs affect consciousness only and are devoid of analgesic activity (exception ketamine). The effect cannot be ascribed to nonselective binding to neuronal cell membranes, although this may hold for propofol... 

Changes in adrenergic function are complex. Inhibition of neuronal catecholamine reuptake gives rise to superimposed indirect sympathomimetic stimulation. Patients are supersensitive to catecholamines (e.g., epinephrine in local anesthetic injections must be avoided). On the other hand, blockade of ai-receptors may lead to orthostatic hypotension. 

As agents blocking conductivity in axons and dendrites, local anesthetics differ from the compounds that block neuron transmission in synapses. 

A mechanism of local anesthetic action in which they serve as sodium channel blockers has been proposed. According to this mechanism, the molecular targets of local anesthetic action are the voltage-requiring sodium channels, which are present in all the neurons. The process of local anesthesia by respective drugs can be schematically represented in the following manner. 

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