Lokalan�sthetika

Abstract

Local anesthetics provoke reversible blockade of nerves by interaction with sodium channels in membranes of nerves. The uncharged molecular configuration of the local anesthetic penetrates the membrane from the outside and the charged configuration then interacts with the sodium channel from the inside. The potency of a local anesthetic is determined mainly by lipid solubility, the time of onset by the pK(a) of the substance and the duration of action by protein binding. Local anesthetic molecules consist of a hydrophilic tertiary amine and a lipophilic aromatic system combined by an ester or amide linkage. Local anesthetics may therefore be classified as aminoester or aminoamide compounds. Aminoesters are hydrolysed by plasmacholinesterase whereas aminoamides undergo metabolisation in the liver. Aminoamides cause fewer allergic reactions. Local anesthetics show dose-dependent CNS and cardiac toxicity. Reports of toxicity, mainly involving bupivacaine and etidocaine initiated the development of ropivacaine which is the first aminoamide marketed as a pure S-enantiomer. Recently introduced was levo-bupivacaine, the S-enantiomer of bupivacaine.

Synthesis of α-amino amides via α-amino imidoylbenzotriazoles

“…a-Amino amides are important synthetic targets as the smallest subunit of naturally occurring peptides and proteins. 1 a-Amino amides have been claimed as antiinflammatory, 2 antibacterial, 3 anticonvulsant, 4 and cerebro-protective 5 agents, and utilized as local anesthetics, 6 analgesics, 7 and melanocortin agonists. 8 Available methods for the synthesis of a-amino amides 1 include (Scheme 1): (i) hydrolysis of a-amino nitriles 2; 9,10 (ii) multicomponent Ugi reactions (the four-component variant is shown); 11 reactions of amines with (iii) benzotriazol-l-yl a-amino esters 3 (Y = -OBt) 12 or a-aminoacyl benzotriazoles 3 (Y = Bt), 13,14 (iv) mixed anhydrides 4, 15,16 (v) a-bromo amides 5, 17,18 or (vi) aziridinones 6; 19 (vii) reactions of dichloroacetamide 7 with amines and benzotriazole followed by nucleophilic substitution of benzotriazolyl group in 8; 20 reactions of dimethylcarbamoylsilane 9 with (viii) iminium salts, 21 or (ix) with imines in the presence of boron trifluoride etherate; 22 and (x) Pd-catalyzed double carbohydroamination of iodoarenes.…”

Liposomal bupivacaine: a review of a new bupivacaine formulation

“…It has a pKa of 8.1 so only 15% is present in uncharged form at tissue pH. The uncharged fraction of bupivacaine travels across the cell membrane of the nerve, and once charged binds to the inner side of sodium channels, inactivating them 20. The release of bupivacaine from its binding site is slow, which leads to a longer duration of action than lidocaine 21…”

Uterine contractility changes in a perfused swine uterus model induced by local anesthetics procaine, lidocaine, and ropivacaine

“…LAs of the ester type, such as procaine and tetracaine, are degraded at the site of application in humans, catalyzed by the ubiquitous cholinesterase producing defined metabolites. LAs of the amide type (lidocaine, bupivacaine, ropivacaine and many more) remain unmodified and are excreted through the kidney, or are transported to the liver where they are metabolized [15]. We hypothesize that the molecular structure of LAs influences their effect on contractility.…”