Electrophysiological demonstration of both alpha 2-agonist and antagonist properties of RX 781094.

The effects of RX 781094, a new and potent alpha 2-adrenoceptor antagonist, on locus coeruleus (LC) unit activity were examined. Low doses of RX 781094 produced suppression of spontaneous LC unit activity which could be reversed with yohimbine. The increase in LC firing produced by WB 4101 could also be reversed with a low dose of RX 781094. Thus, at low doses, RX 781094 has clonidine-like alpha 2-agonist activity. At higher doses, RX 781094 reversed the effects of clonidine and markedly shifted the dose of clonidine required to suppress LC unit activity. These data suggest that at high doses RX 781094 has alpha 2-antagonist properties. It is concluded that RX 781094 may be a partial agonist at alpha 2-adrenoceptors in the CNS.