Local anesthetics chemical structure

Therapeutic Function Local anesthetic Chemical Name dl-l-Butyl-2, 6 -pipecoloxylidide Common Name -Structural Formula ... 

Chemical structure of cocaine and synthetic local anesthetics. 

Characteristics of chemical structure. Local anesthetics possess a uniform structure. Generally they are secondary or tertiary amines. The nitrogen is linked through an intermediary chain to a lipophiUc moiety—most often an aromatic ring systenx... 

It is interesting that a nnmber of antihistamine, anticholinergic, and adrenergenic drngs having analogous chemical structures, also exhibit local anesthetic properties. It is possible that by interacting with internal axoplasmic membranes, they rednce the ion flow in particnlar, the flow of sodinm ions inside nerve cells. 

Encainide Encainide, 4-methoxy-N-[2-[2-(l-methyl-2-piperidinyl)ethyl]phenyl]-benza-mide (18.1.15), is synthesized by acylating 2-(l-methyl-2-piperidylethyl)aniline with 4-methoxybenzoic acid chloride. The chemical structure of encainide is substantially different than other local anesthetics and antiarrhythmics [25-27]. 

Many substances of widely different chemical structure abolish the excitability of nerve fibers on local application in concentrations that do not cause permanent injury and that may not affect other tissues. Sensory nerve fibers are most susceptible, so that these agents produce a selective sensory paralysis, which is utilized especially to suppress the pain of surgical operation. This property was first discovered in cocaine, but because of its toxicity and addiction liability, it has been largely displaced by synthetic chemicals. The oldest of these, procaine (novocaine), is still the most widely used. Its relatively low toxicity renders it especially useful for injections, but it is not readily absorbed from intact mucous membranes and is therefore not very effective for them. Many of its chemical derivatives are also used. They differ in penetration, toxicity, irritation, and local injury as well as in duration of action and potency. Absolute potency is not so important for practical use as is its balance with the other qualities. If cocaine is absorbed in sufficient quantity, it produces complex systemic actions, involving stimulation and paralysis of various parts of the CNS. These are mainly of toxicological and scientific interest. Its continued use leads to the formation of a habit, resembling morphinism. This is not the case with the other local anesthetics. 

The additional rejected claims, 2-8, were directed to additional, presumably narrower embodiments of claim 1. In rejecting claims 1-8 for alleged obviousness, the USPTO examiner (and majority of the USPTO Board that upheld the rejection) relied on a single piece of prior art from the chemical literature.26 The cited art related to a study of the local anesthetic properties of certain carbazoles, dibenzofurans, and dibenzothiophene derivatives. There were no bis-basic esters of carbazoles disclosed (only mono-basic esters), but there was one bis-basic ester of a dibenzofuran that was disclosed, having the structure shown in Figure 8.2. 

Hypersensitivity to local anesthetics appears to be related to both chemical structure and the method of administration. Allergic reactions occur most frequently with csler-ba.sed local anesthetic agents (benzoic acid derivatives). Adverse effects include allergic dermatitis, asthmatic attack, or. in extreme cases, death due to anaphylactic shock. Individuals suffering a hypersensitive reaction from one local anesthetic agent are often sensitive to compounds with a. similar structure. For example, patients semsilive to procaine arc often also sensitive to amethocaine... 

Figure 1 Chemical structures for (a) the amide-linked local anesthetics and (b) the ester-linked local anesthetics.

Synonyms Dilocaine Lidoderm Lidoject-1 Lignocaine Nervocaine Nulicaine Octocaine Solarcaine Xylocaine Xylocard Chemical/Pharmaceutical/Other Class Amide-type local anesthetic Class IB antiarrhythmic Chemical Structure ... 

Pramoxine hydrochloride (anusol, tronothane, others) is a surface anesthetic agent that is not a benzoate ester. Its distinct chemical structure may help minimize the danger of crosssensitivity reactions in patients allergic to other local anesthetics. Pramoxine produces satisfactory surface anesthesia and is reasonably well tolerated on the skin and mucous membranes. It is too irritating to be used on the eye or in the nose. 

Since the discovery of cocaine in 1880 as a surgical local anesthetic, several thousand new compounds have been tested and found to produce anesthesia by blocking nerve conductance. Among these agents, oniy approximateiy 20 are ciinicaiiy available in the United States as local anesthetic preparations (Tabie 16.1). Tabie 16.2 contains chemical structures of the different types of agents in current or recent use. 

Both of these groups are highly lipophilic and appear to play an important role in the binding of local anesthetics to the channel receptor proteins. Structural modification of this portion of the molecule has a profound effect on its physical and chemical properties, which in turn alters its local anesthetic properties. 

Local anesthetics are widely used in many primary care settings. Techniques for their administration in these settings include topical application, local infiltration, field block, and peripheral nerve block. Their use can be maximized by an understanding of their potencies, durations of action, routes of administration, and their pharmacokinetic and side effect profiles. The generic, trade name, and recommended application are given in Table 16.1, and the chemical structures of these agents can be found in Table 16.2. 

Local anesthetics are divided into two groups according to their basic chemical structure. These are esters and amides. An ester is a chemical compound formed from the reaction between an acid and an alcohol. Amides are an oiganic chemical compound formed by reaction of an acid chloride, acid anhydride, or ester with an amine. Amides have a lower incidence of causing an allergic reaction than esters. 

The Erythrophleum alkaloids represent a clearly defined class, both as regards their chemical structure and pharmacological properties. They are alkamine esters of monocarboxylic acids of the diterpene series and possess remarkable cardiac activity of the digitalis type coupled with very intense local anesthetic action. 

These local anesthetics, including lidocaine (Xylocaine), mepivacaine (Carbo-caine), Prilocaine (Citanest), and bupivacaine (Marcaine) are weak sensitizers, but allergic reactions are sporadically reported, e. g., lidocaine (Turner 1977). Recently Fregert et al. (1979) described two patients developing lidocaine allergy after 8 and 1 month use of Xyloproct ointment (lidocaine 5%, hydrocortisone acetate) they also had positive patch tests to related amide anesthetics, both to mepivacaine, one to bupivacaine and prilocaine. A positive reaction to the chemically unrelated cincaine was interpreted as concomitant sensitivity rather than cross-sensitivity. Safe substitutes for benzocaine-sensitive patients include lidocaine, mepivacaine, prilocaine, bupivacaine, and pyrocaine (Fisher 1973 p. 312), all based on an amide structure. Lidocaine-sensitive patients may use tetracaine (pontocaine), a derivative of aminobenzoic acid. 

Fig. 7.21 Chemical structures of two meiin categories of local anesthetics, esters and amides, with some structures of important members of each category...

The relationship between the pharmacological effects elicited by menthol and ion channel dysfunction depends on the interaction of this monoterpene with distinct types of ion channels. In this way, the reported local anesthetic effects attributed to menthol and for some of its structural chemical homologues, such as thymol, carvacrol, and carveol, might be caused by a blockade of voltage-gated sodium channels [21, 25, 26]. On the other hand, a pronounced cytotoxic effect of menthol is correlated with the action of menthol in TRPM8 channels [22, 27]. At this point, we will make a short introduction to TRPM8 channels to further discuss the putative cytotoxic effects of menthol in various cell types. 

One of the first uses of local anesthetics (LA) for anesthesia was in the late nineteenth century with William Halsted reporting a mandibular block and brachial plexus block using cocaine [37,38]. The chemical structure of local anesthetics in clinical use consists of an aromatic (lipophilic) benzene ring linked to an amino group (hydrophflic) via either an ester or an amide intermediate chain. The intermediate link classifies the local anesthetic as either an ester (procaine, chloroprocaine, tetracaine, and cocaine) or an amide (lidocaine, prilocaine, mepivacaine, bupi-vacaine, etidocaine, and ropivacaine). 

Local anesthetics all contain a lipophilic aromatic ring, a hydrophilic tertiary amine and an ester or amide linkage.The general chemical structures of amide and ester anesthetics are illustrated in Figure 64.1. 

Drug Class local anesthetic (amino amide) Chemical Structure see Figure 65.1 Chemical Name l-butyl-N-(2,6-dimethylphe-nyl)piperidine-2-carboxam Cj H gN O... 

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