[Stereochemical aspects of narcotic and psychotropic drug action]

Medicinal drugs are predominantly, whereas narcotic and psychotropic drugs are exclusively exogenous compounds. Three further fundamental properties of the narcotic/psychotropic compounds of significant abuse potential is that they all are of natural (plant or microbial) origin, they contain a large number of chiral atoms, and they influence the neurotransmission processes in the central nervous system. For some of them, the existence of corresponding endogenous ligands have recently been reported. Since exogenous compounds and their endogenous ligands are assumed to bind the same target moiety of the receptor, several fundamental questions arise: To what extent can stereochemical relationships be established between the exogenous compound and its endogenous counterpart? Do they have superimposable moieties? Are the corresponding chiral atoms of the same configuration? Is there a chiral-genetic relationship between the exogenous and endogenous compound? Theoretical aspects and answers to all these questions are sought for morphine, cocaine, LSD, tetrahydrocannabinol, amphetamine and related molecules.