Selective influence of ergot alkaloids on cortical and striatal dopaminergic and sergotonergic receptors

The ergot alkaloids studied do exert selective effects on monoamine receptor systems. Lisuride acts as a very potent stimulator of adenylate cyclase in cortical brain regions, and may function as a mixed agonist-antagonist at high concentrations. It is most likely that in cortex, lisuride effects both dopamine and serotonin receptors, but predominantly serotonin receptors coupled to adenylate cyclase. The antagonist molindone exhibits selectivity for cortical serotonin-stimulated cyclase versus dopamine-stimulated cyclase and may prove useful for further elucidating the sites of lisuride action. LSD interacts with serotonin-stimulated cortical adenylate cyclase at higher concentrations than are needed for lisuride stimulation but, nevertheless, at lower concentrations than for serotonin itself (2-4). Bromocriptine, lergotrile and ergonovine may also act as agonists in stimulating adenylate cyclase, but with considerably less potency, and with differences in regional specificity for this stimulation, from lisuride and LSD. Each of these ergots may act as a mixed agonist-antagonist at high concentrations. With respect to the regions studied, antagonist effects on cyclase appear to be more prominent in striatum than in the cortical regions. The greater specificity of lisuride for serotonergic cortical receptors should make this compound useful in further studies of this system.