Lidocaine structure

Local anesthetics interact with peripheral nerve cell membranes and exert a pharmacological effect [34]. Potential oscillation was measured in the presence of 20 mM hydrochlorides of procaine, lidocaine, tetracaine, and dibucaine (structures shown in Fig. 16) [19]. Amplitude and the oscillatory and induction periods changed, the extent depending on the... 

FIG. 16 Chemical structures of (a) procaine hydrochloride, (b) lidocaine hydrochloride, (c) tetracaine hydrochloride, and (d) dibucaine hydrochloride. 

FIG. 1 Molecular structures of the drugs examined in the delivery study the general anesthetics, alkanols (I), halothane (II), enflurane (III), isoflurane (IV), halogenated cyclobutane (V) the local anesthetics, dibucaine hydrochloride (VI), procaine hydrochloride (VII), tetracaine hydrochloride (VIII), lidocaine hydrochloride (IX), benzyl alcohol (X) the endocrine disruptor, bisphenol A (XI), and alkylbenzenes, benzene (XII), toluene (XIII), ethylbenzene (XIV), and propylbenzene (XV). 

Nonprescription topical anesthetics such as lidocaine and benzocaine are available in many types of products. Local anesthetics decrease discharges in superficial somatic nerves and cause numbness on the skin surface but do not penetrate deeper structures such as muscle where the pain often lies. 

Licensing event reports (LERs), for nuclear power facilities, 7 7 539 Lichens, in nitrogen fixation, 7 7 299 Licuri wax, 26 210-211 Lidesthesin, molecular formula and structure, 5 9 It Lidocaine, 5 100... 

The major metabolites of lidocaine formed from this part of the molecule are the amine (16), which is further oxidized to the para-phenol, N-dealkylation of the parent drug with loss of acetaldehyde to form the secondary amine, and a second N-dealkylation to form the primary amine (structure not shown). Although there are only a few major metabolites of lidocaine, with sensitive analytical methods it is likely that hundreds of minor metabolites could be detected. 

Mueller-Goymann, C.C., and Frank, S.G., Interaction of lidocaine and lidocaine-hydrochloride with the liquid crystal structure of topical preparations, Int. J. Pharm., 29 147-159 (1986). 

Mechanism - Structurally like lidocaine, mexiletine inhibits the inward sodium current, thus reducing the rate of rise of the action potential. Phase 0. Mexiletine decreases the effective refractory period (ERP) in Purkinje fibers. The decrease in ERP is of lesser magnitude than the decrease in action potential duration (APD), with a resulting increase in ERP/APD ratio. 

Tocainide (Tonocard) is an orally effective antiarrhyth-mic agent with close structural similarities to lidocaine. 

Figure 5.4 Structural formulae showing tertiary (lidocaine (lignocaine), bupivacaine) and secondary (prilocaine) amines. Asymmetrical carbon atom.

The class lb antiarrhythmic drug mexilitine is structurally related to the local anesthetic agent lidocaine and also shows a voltage- and frequency-dependent block of sodium channels. Mexilitine is not selective for any painrelevant subtype of sodium channel. As an advantage over lidocaine, mexilitine can be given orally. 

FIGURE 12-1 Structure of lidocaine. The basic structure of a lipophilic and hydrophilic group connected by an intermediate chain is common to most local anesthetics. 

Leuwer M, Haeseler G, Hecker H, et al. An improved model for the binding of lidocaine and structurally related local anaesthetics to fast-inactivated voltage-operated sodium channels, showing evidence of coop-erativity. Br JPharmacol. 2004 141 47-54. 

A frequently cited example of an important natural-product-derived drag is the neuromuscular blocker d-tubocurarine, derived from the South American plant curare, which was used by South American Indians as an arrow poison (see Chapter 26). Tubocurarine led to the development of decamethonium, which, although structurally dissimilar to tubocurarine, was nevertheless synthesized based on the then prevalent presumption that tubocurarine contained two quaternary nitrogens. Similarly, synthetic local anesthetics, such as lidocaine, benzocaine, and dibucaine, were synthesized to mimic the nerve-blocking effect of cocaine, a natural alkaloid obtained from the leaves of Coca eroxylum, but without the adverse side effects that have led to its abuse. 

Just like sodium ions, chloride ions are spectator ions in acid-base chemistry. Their job is to provide a charge balance to the cations in solution. So, in calculating the pH of lidocaine hydrochloride we ignore the chloride ion. Now we could draw out the structure or write the molecular formula of lidocaine and its conjugate acid, but it is tedious to do so. Let s do what most chemists do, and postulate a temporary abbreviation for these species. How about using L for lidocaine, and HL+ for its conjugate acid Now, we can write an equation for the acid ionization equilibrium reaction. 

Mechanism of action. Na -channel blocking antiarrhythmics resemble most local anesthetics in being cationic amphiphilic molecules (p.206 exception phenytoin, p.191). Possible molecular mechanisms of their inhibitory effects are outlined on p.202 in more detail. Their low structural specificity is reflected by a low selectivity toward different cation channels. Besides the Na channel. Carotid 1C channels are also likely to be blocked. Accordingly, cationic amphiphilic antiarrhythmics affect both the depolarization and repolarization phases. Depending on the substance, AP duration can be increased (Class IA), decreased (Class IB), or remain the same (Class IC). Antiarrhythmics representative of these categories include Class IA—quinidine, procainamide, ajmaline, disopyramide Class IB—lidocaine, mexile-tine, tocainide Class IC—flecainide, propafenone. 

Lidocaine is structurally similar to cocaine, which was the first clinically useful local anaesthetic (Figure 5.4). The stimulating effect of cocaine, however, is due to its effect on a second, different receptor in the brain that indirectly amplifies the effect of dopamine and norepinephrine (we will deal with this matter in a later lecture). This effect is actually observed at concentrations lower than those required for the blocking of sodium channels. Yet, local application of cocaine will result in very high concentrations that will... 

Singh, P. and Roberts, M. S. Iontophoretic transdermal delivery of salicylic acid and lidocaine to local subcutaneous structures. J. Pharm. Sci. 82 127, 1993. 

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