Drugs that reversibly depress neuronal function with accompanying loss of pain perception (ANALGESIA) and/or other sensations (anti-nociceptive; see NOCICEPTION). Drugs that induce a state of ANAESTHESIA fall into three main categories. (1) General: an agent that abolishes CONSCIOUSNESS and perception of all sensations. (2) Local: an agent whose anaesthetic action is limited to an area of the body determined by the site of its application. (3) Topical: a LOCAL ANAESTHETIC applied directly to the area to be anaesthetised, usually the mucous membranes or the skin.
Two main classes of general anaesthetics are non-specific agents that depress excitable tissue at all levels of the CNS and receptor-specific agents that have an action at specific neuro-transmitter receptor sites in the CNS. Non-specific agents include inhalational VOLATILE ANAESTHETICS (including HALOTHANE, enflurane, methoxyflurane and isoflurane) and other agents (such as NITROUS OXIDE, CHLOROFORM, cyclopropane, and diethyl ETHER). Volatile anaesthetics are combined typically with an ADJUVANT such as nitrous oxide to induce clinical (human) anaesthesia.
The mechanisms of action for these compounds remain unknown but is thought to involve a dose-dependent reduction in the metabolic rates of certain neurons in the CNS. In contrast to non-specific anaesthetics, general anaesthesia can be produced only with a combination of several receptor-specific agents. The main component is either one of the opioid NARCOTICS (such as FENTANYL) or one of the BARBITURATES (for instance THIOPENTAL) to induce sedation, analgesia, and reduced autonomic response, and may be given in combination with a BENZODIAZEPINE (for example DIAZEPAM) to decrease awareness during NARCOSIS. Opioid analgesics may also be combined with NEUROLEPTIC compounds to reduce motor activity and ANXIETY together with CURARE-like agents to suppress movement. Compounds used almost exclusively in experimental animal research to induce surgical anaesthesia include urethane, CHLORAL HYDRATE, CHLORALOSE, XYLAZINE, and KETAMINE. The second and third category of anaesthetics include the short-acting local anaesthetics (for instance LIDOCAINE, PROCAINE and COCAINE) and long-acting ION CHANNELNEUROTOXINS (such as TETRODOTOXIN and saxitoxin). These drugs are used mainly to interrupt nerve transmission of pain sensations when applied locally to nerve tissue in appropriate concentrations. Local anaesthetics act selectively at the level of the neuronal cell body to prevent transient increases in sodium ion channel permeability and to reduce potassium permeability at rest. The cell THRESHOLD of excitation is increased resulting in a blockade of both the generation and the conduction of any ACTION POTENTIAL.
