Effects of 4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline Hydrochloride (BE 6143) at pre- and postsynaptic alpha-adrenoceptors in rabbit aorta and pulmonary artery.
Strips of rabbit aorta and pulmonary artery were used to study the effects of 4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline hydrochloride (BE 6143 or BDF 6143) on pre- and postsynaptic alpha-adrenoceptors. BE 6143 caused contraction of both preparations with a potency slightly higher than and an intrinsic activity 0.7-0.8 that of phenylephrine. The effect was competitively antagonized by prazosin and rauwolscine. Conversely, BE 6143 antagonized contractile responses to phenylephrine, alpha-methylnoradrenaline and noradrenaline (norepinephrine) with pA2 values of 7.1-7.4. In strips preincubated with 3H-noradrenaline and then superfused, BE 6143 increased the electrically evoked overflow of tritium. Increases by 30% were produced by concentrations of about 1.5 nmol/l; high concentrations failed to change or even reduced the evoked overflow. BE 614 0.01 mumol/l also increased electrically evoked contractions whereas high concentrations were inhibitory. The drug shifted the log concentration-response curve of clonidine for inhibition of evoked tritium overflow to the right in parallel manner; from the shift, a pA2 value of 8.3 was calculated. When presynaptic alpha-adrenoceptors had been blocked by yohimbine or rauwolscine, BE 6143 0.01-10 mumol/l caused a decrease in evoked tritium overflow which was more pronounced, the higher the concentration of yohimbine or rauwolscine. It is concluded that BE 6143 acts as a partial agonist at the postsynaptic alpha 1-adrenoceptors and as an antagonist at the presynaptic alpha 2-receptors of rabbit aorta and pulmonary artery. It has higher affinity pre- than postsynaptically, and its affinity for the presynaptic receptors exceeds that of yohimbine and rauwolscine. In addition, however, BE 6143 inhibits the release of noradrenaline by a non-alpha-adrenergic mechanism.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D054833:Isoindoles; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D007093:Imidazoles; D054833:Isoindoles; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; C036966:4-chloro-2-(2-imidazolin-2-ylamino)isoindoline; D003000:Clonidine; D009638:Norepinephrine