Potent dopamine agonist activity of a novel ergoline, 6-ethyl-9-oxaergoline (EOE).
6-Ethyl-9-oxaergoline (EOE) and its enantiomers were compared with apomorphine in a number of tests designed to measure dopamine (DA) agonist activity within the central nervous system. In rats, the tests were: interaction with DA receptors labeled with 3H-apomorphine or 3H-spiroperidol; the effects on DA synthesis as assessed by the gamma-butyrolactone procedure; turning in 6-OHDA lesioned animals; stereotypy; and, slowing of DA cell firing rates. In the mouse, locomotor activity, hypothermia and postural asymmetry in caudectomized animals were studied. Emesis in the beagle was also examined. The (-)-enantiomer of EOE was more potent than either the (+)-enantiomer or the racemate in all tests. With the exception of inducing stereotypy and the displacement of 3H-apomorphine from rat striatal membranes, (-)-EOE was equi- or more potent than apomorphine in all test procedures. (-)-EOE was effective following oral administration and exhibited a longer duration of action than apomorphine. The results indicate EOE is a potent DA agonist.
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004873:Ergolines / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects
D004873:Ergolines; D011954:Receptors, Dopamine; C034945:6-ethyl-9-oxaergoline; D001058:Apomorphine; D015107:4-Butyrolactone; D004298:Dopamine