A comparison of peripheral pre- and postsynaptic alpha 2-adrenoreceptors using meta-substituted imidazolidines

1 The cardiac presynaptic activity, as derived from the inhibition of tachycardia to electrical stimulation of the cardiac sympathetic nerve in pithed, normotensive rats of 8 meta-substituted phenyl(imino)imidazolidines (2, 3- and 2,5- derivation) was determined. 2 The agonistic activity of the imidazolidines was measured with respect to vascular alpha 1- and alpha 2-adrenoreceptors. Accordingly, the increase in diastolic pressure of pithed, normotensive rats to intravenous administration of the imidazolidines was evaluated after pretreatment with 5% w/v glucose solution, yohimbine (1 mg/kg), prazosin (0.1 mg/kg) and the combination of both alpha-adrenoreceptor antagonists. 3 With respect to pre- and postsynaptic alpha 2-adrenoreceptors the 2,5-substituted derivatives were generally less active than the corresponding 2,3-substituted isomers. The steric bulk of the substituent at the 5-position of the imidazolidine molecule appeared to govern the activity with respect to cardiac presynaptic alpha 2-adrenoreceptors, whereas no such clear relationship could be derived for the activity on vascular postsynaptic alpha 2-adrenoreceptors. This indicates that there exists a close resemblance between pre- and post-synaptically located alpha 2-adrenoreceptors. However, these receptor sites are not identical.