Antagonism of noradrenaline and histamine by desipramine in the isolated artery of the rabbit ear.

1. The effects of desipramine (DMI) were examined on the vasoconstrictor responses of the isolated perfused artery of the rabbit ear to noradrenaline (NA) and to histamine. Innervated and sympathetically denervated arteries were used.2. In innervated arteries, DMI in concentrations of 1 x 10(-8) to 1 x 10(-7)M enhanced the responses to NA; higher concentrations reduced the responses. In sympathetically denervated arteries, DMI caused only reduction of the responses to NA.3. Responses to histamine were reduced by DMI in both innervated and denervated arteries. DMI was considerably more potent as an antagonist of histamine than of noradrenaline.4. The reduction by DMI of the responses to NA and histamine in both innervated and denervated arteries was associated with a parallel shift to the right of the concentration-response curves of the agonist and a depression of the maximal response. These effects of DMI were reversible.5. Analysis of the data by the method of Arunlakshana & Schild (1959) showed the following: the antagonism of the action of NA by DMI on denervated arteries fulfilled the requirements for competitive antagonism; antagonism of the action of NA on innervated arteries was not competitive; antagonism of the actions of histamine on innervated and denervated arteries was not competitive.6. It is suggested that DMI antagonizes the action of NA and histamine on the perfused artery of the rabbit ear in two ways: (i) reversible specific antagonism which is competitive for NA and not competitive for histamine; (ii) reversible non-specific antagonism which is non-competitive for both agonists.