Effects of phenyl-2-aminoethyl sulfide, a novel dopamine-beta-hydroxylase substrate, on the cardiovascular system of the anesthetized dog.
In previous work we have established that phenyl-2-aminoethyl sulfide (PAES) is a novel substrate for dopamine-beta-hydroxylase (DBH) which is stereospecifically oxygenated by the enzyme to the corresponding sulfoxide, (S)-phenyl-2-aminoethyl sulfoxide (PAESO). We now report that PAES possesses very little, if any, direct adrenergic agonist activity, but exhibits indirect sympathomimetic activity at relatively high doses (approximately 4 mg/kg). This assertion, that PAES is a new indirect sympathomimetic, is supported by our finding that pretreatment with cocaine completely abolishes the sympathomimetic activity of PAES. Furthermore, the effects of PAES are diminished with consecutive administration. In addition to its indirect sympathomimetic activity, we have also observed that PAES infusion almost completely blocks the reflex response elicited by hydralazine, a direct vasodilator. In contrast, we have found that PAESO possesses neither direct nor indirect sympathomimetic activity at doses as high as 6 mg/kg. Since PAES should be readily converted in vivo into PAESO, the implications of these findings in terms of potential antihypertensive action of PAES are discussed.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004299:Dopamine beta-Hydroxylase; D005021:Ethylamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007263:Infusions, Parenteral; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013566:Sympathomimetics / Q000494:pharmacology*
D005021:Ethylamines; D013566:Sympathomimetics; C039557:phenyl-2-aminoethyl sulfide; D004299:Dopamine beta-Hydroxylase