Biochemical, behavioural, and endocrine effects of CK 204-933, a novel 8 beta-ergolene.
CK 204-933 displaces [3H]dopamine and [3H]spiperone with high affinity from D-1 and D-2 recognition sites in membranes of calf caudate. Results from functional in vitro tests suggest that it is a partial agonist at D-1 receptors and an antagonist at D-2 receptors. These opposite effects at dopamine receptor subtypes are also expressed in vivo. For instance, in 6-hydroxydopamine lesioned rats, CK 204-933 induces contralateral rotations which are antagonised by SCH 23390 but not by sulpiride. On the other hand, CK 204-933 induces a long lasting increase of dopamine turnover in rat striatum and antagonises apomorphine-induced gnawing behaviour in rats. CK 204-933 increases prolactin serum levels in rats after subcutaneous administration, whereas after oral administration a moderate decrease of prolactin serum levels was seen. The latter effect is probably due to the formation of active metabolites. CK 204-933 exhibits also a high affinity to [3H]prazosin binding sites and antagonises serotonin-mediated stimulation of adenylate cyclase in rat hippocampus. On the other hand, CK 204-933 has no effect of only very weak effects on noradrenaline and serotonin release from rat cerebral cortex slices, which is consistent with its weak effects on noradrenaline- and serotonin-turnover in rat brain. Based on these properties it is suggested that CK 204-933 could be of therapeutic value in brain diseases associated with disturbances of monoaminergic neurotransmission.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D004873:Ergolines / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology
D018492:Dopamine Antagonists; D004873:Ergolines; D018377:Neurotransmitter Agents; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D011388:Prolactin; C053616:CK 204-933; D000242:Cyclic AMP; D004298:Dopamine; D009638:Norepinephrine