Potent dopamine agonist activity of a novel ergoline, 6-ethyl-9-oxaergoline (EOE)

• Published in: Life sciences (1973) Vol. 30; no. 21; p. 1847
• Main Authors: Martin, G E, Williams, M, Clineschmidt, B V, Yarbrough, G G, Jones, J H, Haubrich, D R
• Format: Journal Article
• Language: English
• Published: Netherlands 24.05.1982
• Subjects: 4-Butyrolactone - pharmacology; Animals; Apomorphine - pharmacology; Brain - drug effects; Brain - metabolism; Dopamine - metabolism; Ergolines - metabolism; Ergolines - pharmacology; Female; Humans; Hypothermia - chemically induced; Mice; Motor Activity - drug effects; Rats; Rats, Inbred Strains; Receptors, Dopamine - metabolism; Stereoisomerism; Stereotyped Behavior - drug effects
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(82)90323-X

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.