Evidence that the purported dopaminergic agonist (3,4-dihydroxyphenylimino)-2-imidazolidine (DPI) may reduce rat striatal dopamine turnover by an alpha 2-adrenergic mechanism.
The potent alpha-adrenergic agonist DPI, which has also been claimed to be a selective dopaminergic agonist, was shown to reduce rat striatal dopamine (DA) synthesis, DA utilization and DA metabolism following intraperitoneal administration (25 mumol/kg). An analytical procedure for the determination of DPI was developed and its application showed that DPI did not penetrate into the brain in substantial amounts. The possibility of a direct stimulatory action upon striatal presynaptic DA receptors was excluded by the demonstration that DPI lacked effectiveness both in the gamma-butyrolactone model and following intrastriatal administration. The selective alpha-adrenergic agonists phenylephrine (alpha 1) and tramazoline (alpha 2) decreased and increased DA metabolism, respectively, the yohimbine-induced increase being antagonized by DPI. The carbon-bridge analogue (3,4-dihydroxybenzyl)-2-imidazoline (DHBI) had about the same activity as DPI, whereas the potential DPI metabolite (4-hydroxy-3-methoxyphenylimino)-2-imidazolidine (HMPI) was without effect upon striatal DA metabolism. The results are discussed in relation to the remarkable resemblance with the literature data concerning clonidine. It is concluded that the DPI-elicited attenuation of striatal DA turnover is, in all likelihood, the result of a stimulation of alpha 2-adrenoceptors possibly located within the central nervous system. The results cast some doubt on the designation of DPI as a selective DA-inhibitory receptor agonist.
D015107:4-Butyrolactone / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D048288:Imidazolines; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D002396:Catechols; D048288:Imidazolines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; C022804:(3,4-dihydroxybenzyl)-2-imidazoline; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline; D003000:Clonidine; D015107:4-Butyrolactone; D004298:Dopamine; D009638:Norepinephrine