Presynaptic inhibition by ergotamine of the responses to cardioaccelerator nerve stimulations in the cat.

The effects of ergotamine on the tachycardia elicited by postganglionic stimulation of the cardioaccelerator nerve have been investigated in both intact and spinal (desmethylimipramine-pretreated) cats. Ergotamine (2.5--20 microgram kg-1) selectively antagonized the response to low-frequency (0.3--3 Hz) stimulation. The responses elicited by stimulation of the nerve with higher frequencies (greater than 10 Hz) either remained unaltered or were facilitatated by the drug. Pretreatment of the cats with pimozide (0.2 mg kg-1) completely antagonized the inhibitory effects of ergotamine on the sympathetic neuron. Although phentolamine (0.5 mg kg-1) did appear to attenuate the effects of ergotamine, the changes were, however, not statistically significant. Since the drug did not reduce the cardiac effects of isoprenaline or tyramine, it is concluded that ergotamine interferes with the release of noradrenaline from the cardioaccelerator nerve, mainly by stimulating the presynaptic dopaminergic receptors. This effect may be an important mechanism by which the drug causes bradycardia in almost all species regardless of the blood pressure response.