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.
D000818:Animals; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D007093:Imidazoles; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011224:Prazosin