Carbamates I, II and III of the 1,2-dihydroquinoline series have been recently shown to induce selective irreversible inhibition of the catecholamine α-receptors. These compounds bear no discernible analogy to known adrenergic blockers. Only the pseudobase III possesses the required chemical reactivity for covalent bond induction at the receptor level. On the other hand, I and II react spontaneously with molecular oxygen to give the peroxide IV, which possesses chemical reactivity similar to that of III. The hypothesis offers itself that I and II undergo oxidation in vivo in position 2 prior to inhibiting the α-receptor. Pseudobase III has been shown to act as an excellent peptide bond-forming reagent by way of a selective activation of carboxyl functions. This property suggested that III may act as a selective modifier of those esterases which include a carboxyl function as part of their active centre. With acetylcholinesterase (AChE), enzymatic activity toward acetylcholine is abolished by III by way of a mechanism implicating the obliteration of the anionic binding site. The thus modified enzyme retains its esteratic activity toward indophenyl acetate. Chymotrypsin is also inhibited by III, but spontaneous reactivation was observed. However, subtilisin, which does not carry a carboxyl function on its active sequence suffers only competitive inhibition by III. Carbamates I and II react at a negligible rate with AChE and chymotrypsin, whereas peroxide IV reacts like III with these enzymes. These observations support the hypothesis that the adrenergic α-receptor may bear analogy to the carboxyl" serine hydrolases. © 1969."
