Halothane chemical structure

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. 

The chemical structures of the currently available inhaled anesthetics are shown in Figure 25-1. Nitrous oxide, a gas at ambient temperature and pressure, continues to be an important component of many anesthesia regimens. Halothane, enflurane, isoflurane, desflurane, sevoflurane, and methoxyflurane are volatile liquids. 

That the lipid solubility versus anesthetic potency relationship is not above criticism has been intimated for a number of years by a number of authors. Summaries of the relevant facts and comments are found in the reviews of Halsey and Kaufman . It is only since 1974, however, that the possible importance of polar interactions has become a target of intense discussions. General anesthetics have widely different chemical structures and it has never been possible to classify them on chemical grounds. Xenon, nitrous oxide, ethylene, cyclopropane, ether, chloroform, C Fg, SFg, CFj—CHClj, CFj-CHClBr (halothane), CHjOCF.CHCf, (methoxyflurane) can all exert anesthetic action. (This aspect will be discussed in more detail in the next section). Looking at the formulas of these different molecules it is hard to believe that they all associate with the same site and with the same type of forces. A series of observations have been made in recent years that substantiate this scepticism. 

National Halothane Study/NRC Report (1966) Summary of the national halothane study. Possible association between halothane anesthesia and postoperative hepatic necrosis. Report on the national halothane study of the Committee on Anesthesia, National Academy of Sciences - National Research Council. JAMA 197 775-788 Paronetto F, Popper H (1970) Lymphocyte stimulation induced by halothane in patients with hepatitis following exposure to halothane. N Engl J Med 283 277-280 Paton WDM (1957) Histamine release by compounds of simple chemical structure. Pharmacol Rev 9 269-328... 

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