A quantitative structure-activity relationship study on the inhibitory effects of local anesthetics on sodium flux, phosphoinositide breakdown, and binding to sodium channels.
The inhibitory effects of a series of nonspecific local anesthetics on batrachotoxin-elicited sodium flux, batrachotoxin-elicited phosphoinositide breakdown, and on the binding of [3H]batrachotoxin-A 20 alpha-benzoate to sodium channels in guinea pig cerebral cortical synaptoneurosomes are shown to be well-correlated with the molecular size and the hydrophobic character of the molecules. These correlations lead us to suggest that the drug-receptor interaction involves a dispersion interaction, and that the overall effects of local anesthetics is dependent upon their ability to reach the receptor site.
Gupta
S P
SP
Birla Institute of Technology and Science, Pilani, India.
Gupta
J K
JK
Saha
R N
RN
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000779:Anesthetics, Local; D001496:Batrachotoxins; D010716:Phosphatidylinositols; D015222:Sodium Channels; D012964:Sodium