Interaction of ergot drugs with central monoamine systems: Evidence for a high potential in the treatment of mental and neurological disorders

Biochemical, histochemical and behavioural experiments suggest that many ergot drugs possess dopamine (DA) agonistic activity at the postsynaptic DA receptors. It seems likely that this action of bromocriptine and Lergotrile explains their unique anti-parkinsonian properties. Studies of DA-sensitive adenylate cyclase reveal only 10-30% increases of adenylate cyclase activity in striatum. It may, thus, be that small increases in adenylate cyclase activity may be sufficient to produce enhancement of DA neurotransmission in the brain. In agreement it was found that the increase caused by agroclavine in adenylate cyclase activity is significantly enhanced in denervated striata. With low concentrations of ergot drugs a positive interaction was found with DA at the level of the adenylate cyclase. Of all the ergots tested for DA agonistic activity agroclavine and elymoclavine were found to be the most potent in all models studied. The ergoline derivative CF 25-397, unlike bromocriptine and Lergotrile, does not seem to possess anti-parkinsonian activity (Calne, personal commun.). It is therefore of interest to point out that CF 25-397 differed from bromocriptine and Lergotrile in its action on dopaminergic mechanisms. Thus, it did not reduce DA turnover in the large neostriatal DA system and did not produce stereotyped behaviour. These findings indicate lack of effects of CF 25-397 on postsynaptic neostriatal DA receptors. Such an action may, thus, be important for anti-parkinsonian activity. In the lower dose range several ergot drugs seemed to preferentially activate DA receptors other than the postsynaptic DA receptors in the forebrain, e.g., the autoreceptors of the DA nerve cells. Some ergot drugs such as methergoline possess preferential effects on 5-HT receptors.