The pharmacological characterization of 3,4-dihydroxyphenylimino-2-imidazolidine (DPI) as a potent mixed α1/α2-adrenoceptor agonist rather than as a dopamine receptor agonist

Abstract

Abstract In the past decade many studies have been carried out on the pharmacological actions of the imidazoline derivative DPI (3,4-dihydroxyphenylimino-2-imidazolidine) because it has been proposed as a selective agonist at a postulated subtype of dopamine (DA) receptor. According to the first publication on this concept of multiple DA receptors, authored by Cools & van Rossum (1976), mammalian DA receptors can be divided into excitation-mediating (DAe) and inhibition-mediating (DAi) receptors. DAe receptors appeared to coincide with ‘classical’ DA receptors i.e. those that can be selectively stimulated with apomorphine and inhibited with haloperidol, whereas the newly postulated DAi receptors could be selectively stimulated with DPI and inhibited with ergometrine (Cools & van Rossum 1976, 1980). Though interesting from a conceptual point of view, the idea of the existence of DAi receptors in the mammalian brain was rather speculative, and Cools and coworkers consequently put much effort into attempting to provide it with an experimental basis. They found that in some test models DPI and ergometrine had indeed opposing effects, and they explained these results as being in strong support of the presence of DAi receptors and thus of the validity of the DAe/DAi concept (Cools et al 1976; Cools 1977). In spite of the latter conclusion, however, these authors have repeatedly revised their original concept, i.e. by the additional postulations of the ‘alpha-like norepinephrine receptor’ (Cools & van Rossum 1980) and of the ‘DAi/e receptor’ (Cools 1981).