Monophenolic (2-(dipropylamino)
indans and related compounds have been synthesized and tested for central
dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and
emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the three different
dopamine-receptor mediated effects measured. 4-Hydroxy-2-(dipropylamino)
indan was the most potent of the new compounds. The corresponding 5-hydroxy analogue was less active. 4-Hydroxy-2-[(dipropylamino)methyl]
indan is a new type of dopaminergic agent with a phenylpropylamine moiety in its framework instead of the phenylethylamine structure, common to most
dopamine-receptor agonists. This compound was 10-20 times less active than
apomorphine. 6,7,8,9-Tetrahydro-1-hydroxy-N,N-dipropyl-5H-6-benzocycloheptenylamine and 5-hydroxy-2-[(dipropylamino)methyl]
tetralin were both inactive. Since the intramolecular distances between functional groups in the
indans studied here are different from those in, for example,
apomorphine, it is concluded that a certain variation of these distances can be accepted by the receptor. It could also be demonstrated that the position of the
OH group on the aromatic ring is of importance for the activity and that
emetic activity may be associated with
dopaminergic agonists of the
indan as well as of the
tetralin type of structure.