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.