[Relations between the physico-chemical properties, the chemical reactivity and the local anesthetic activity. 32. (Part 1): Binding capacity of a structural protein (wool) to local anesthetics].
1. The general part deals with the molecular structure of nerve membranes and different local-anesthetic substances as well as the various possibilities of local-anesthetic binding to the nerve membrane. Albumin is usually chosen as a model protein in such investigations, a short extract of which is given. 2. The special part includes the chemical composition and properties of wool macroprotein, the model system used in the present paper. We determined its protein-binding values with cinchocain and tetracain homologues and various known commercial products of local anesthetics (oxybuprocain, parethoxyprocain and tetracain). The binding constants of  these substances on wool protein are shown. 3. A statistically confirmed relationship between the alkyl chain length and the strength of protein binding is given. The free energy per CH2-group ranges between 400 and 500 cal/mol and its larger in cases of low pH values. 4. From the present data, a relationship between the binding constant and the partition constant of each substance of the homologous series studied could easily be observed, which further makes it possible to estimate the characteristic protein-binding constant Kp and also the change in pi-values with the change in free reaction energy of the substances. 5. The large differences in the binding values of the different binding mechanisms, which most probably are dependent on the variable binding affinities of the functional groups as well as on steric factors. But as in the homologous series, only substituents like alkyl amino and alkoxy could be changed, the possibility of some other binding process depending on the alkyl chain length of these groups could not be ruled out. Since the alky groups are non-polar, hydrophobic binding plays a role.
D000418:Albumins / Q000378:metabolism; D000779:Anesthetics, Local / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D003992:Dibucaine / Q000378:metabolism; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*; D011901:Ranvier's Nodes / Q000187:drug effects; D011955:Receptors, Drug; D013329:Structure-Activity Relationship; D013748:Tetracaine / Q000378:metabolism; D014935:Wool
D000418:Albumins; D000779:Anesthetics, Local; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011955:Receptors, Drug; D013748:Tetracaine; D003992:Dibucaine
Beziehungen zwischen den physikalisch-chemischen Eigenschaften, der chemischen Reaktivität und der lokalanästhetischen Wirkung. 32. Mitteilung (1. Teil): Uber das Bindungsvermögen von strukturierten Eiweiss (Wolle) für Lokalanästhetika