AN AB-INITIO STUDY OF HISTAMINE AGONISTS

A systematic theoretical study on histamine agonists and their interac tion with H-1 and H-2 receptor models has been carried out utilizing a b initio molecular orbital technique. The effect of substituents on hi stamine agonists' charge distribution and their agonistic activity has been studied in detail. Drug-receptor interaction models have been st udied at the Hartree Fock level of theory with a split valence basis s et keeping the cost and efficiency of the calculation in mind. The stu dy indicates that the agonistic activity is controlled either by recep tor conformation or by steric hinderances caused by the substituents. The monocationic form of histamine does not appear to be a necessity f or a proton relay process which is similar to the one proposed earlier by Weinstein and coworkers. The study also indicates some importance of common cellular ions in neurotransmitter properties of histamine.