Antihypertensive ergoline derivatives.
Novel ergolines were synthesized and screened in spontaneous hypertensive rats (SHR) with the aim of finding a new class of ergot related antihypertensives. Their prolactin inhibitory effect (measured as nidation inhibition in rats), acute toxicity (LD50) and interference with CNS function (Irwin test) were also evaluated as a measure of selectivity and safety. Modification of the C8 side-chain enhanced antihypertensive activity selectively, while the introduction of substituents in other positions of the ergoline skeleton generally yielded unfavourable results, either by decreasing selectivity or by increasing toxicity.
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D004873:Ergolines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D011388:Prolactin / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D004873:Ergolines; D007555:Isoxazoles; D011720:Pyrazoles; D011743:Pyrimidines; D011388:Prolactin