Anesthetics synaptic transmission

A state of consciousness depends on the intact function of the complex neural networks that underlie alertness, learning and memory. General anesthetics appear to interrupt synaptic transmission within these systems. Multiple ion channels and receptors that mediate and modulate synaptic transmission are putative targets for general anesthetics. All general anesthetics are not alike in the way they alter consciousness. For example, ketamine induces a state of... 

First, it is clear that nearly all drugs with CNS effects act on specific receptors that modulate synaptic transmission. A very few agents such as general anesthetics and alcohol may have nonspecific actions on membranes (although these exceptions are not fully accepted), but even these non-receptor-mediated actions result in demonstrable alterations in synaptic transmission. 

In the past decade, considerable evidence has accumulated that a primary molecular target of general anesthetics is the GABA receptor-chloride channel, a major mediator of inhibitory synaptic transmission. Inhaled anesthetics,... 

In general, there are two broad mechanisms by which the decrease in synaptic transmission is achieved by general anesthetics, either increased inhibitory neurotransmission or decreased excitatory neurotransmission. Many general anesthetics, particularly inhalation anesthetics, appear to act at GABA-A receptors, increasing the sensitivity of the receptors to GABA. This is similar to the effects of the sedative-hypnotic agents, at least at a superficial level, and it results... 

Other tissues The effects of these drugs on the heart are discussed in Chapter 14 (see class I antianhythmic agents). Most local anesthetics also have weak blocking effects on skeletal muscle neuromuscular transmission, but these actions have no clinical application. The mood elevation induced by cocaine probably reflects actions on dopamine or other amine-mediated synaptic transmission in the CNS rather than a local anesthetic action on membranes. 

Lukatch HS, Kiddoo CE, Maciver MB (2005) Anesthetic-induced burst suppression EEG activity requires glutamate-mediated excitatory synaptic transmission. Cereb Cortex 15 1322-1331. 

Bliss, T. V. P., and Lomo, T., 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path, / Physiol. 232 331-356. 

Lukatch HS, Maciver MB (1996) Synaptic mechanisms of thiopental-induced alterations in synchronized cortical activity. Anesthesiology 84 1425-1434 Lukatch HS, Maciver MB (1997) Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro. J Neurophysiol 77 2427-2445 Lukatch HS, Kiddoo CE, Maciver MB (2005) Anesthetic-induced burst suppression EEG activity requires glutamate-mediated excitatory synaptic transmission. Cereb Cortex 15 1322-1331 Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84 87-136... 

Inhalation anesthetics disrupt the normal synaptic transmission process. Many mechanisms of action for anesthetics have been suggested, including the following ... 

Ramirez et al. (82) produced bilateral synaptic blockade within the pre-BotC in pentobarbitone-anesthetized cats by injection of TTX and abolished eupneic ouQ)ut without eliminating the gasping response to severe hypoxia or asphyxia. It is important to note in this regard that Sun and Reis have shown that hypoxic excitation of reticulospinal sympathoexcitatory vasomotor neurons seems to be independent of synaptic transmission, or, at least, TTX-sensitive mechanisms (63,69,70 described above). If similar mechanisms exist in the pre-BotC, the inability of TTX to block hypoxia-induced gasping is not unexpected. 

Richter J, Landau EM, Cohen S. The action of volatile anesthetics and convulsants on synaptic transmission a unified concept. Mo/. Pharmacol 1977 13 548-559. 

When a nerve impulse reaches the synaptic knob the neurotransmitter is ejected into the synaptic cleft and serves as a stimulus to the next adjacent neuron. The vast majority of all impulses transmitted occur at the synaptic gaps, although recent research indicates that chemical transmission can occur at other points along the axon. Many neurological diseases and psychiatric disorders result from a disturbance or alteration of synaptic activity. Drugs such as tranquilizers, anesthetics, nicotine, and caffeine target the synapse and can cause an alteration of impulse transmission. 

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