Effects of cocaine and nortriptyline on contractile responses in rabbit aorta

The effects of cocaine and nortriptyline on contractile responses to field stimulation, (−)-noradrenaline and methoxamine in the rabbit aorta were studied. The method used allowed detection of changes in maximal responses. Cocaine (3.3 × 10−5 M) potentiated all, responses, including maximal responses, to field stimulation, (−)-noradrenaline and methoxamine. Nortriptyline (10−6 M) had no effect on maximal responses to field stimulation, (−)-noradrenaline and methoxamine. The submaximal responses in the presence or absence of nortriptyline were plotted either as a percentage of an initial maximal response to (−)-noradrenaline in the absence of the drug or as a percentage of the maximal response of the individual maximal response. Depending on the method used to express the results, nortriptyline (10−6 M) had no effect or potentiated submaximal responses to field stimulation and had no effect or inhibited submaximal responses to (−)-noradrenaline; this matter is discussed. Nortriptyline (10−6 M) inhibited submaximal responses to methoxamine. The results illustrate that, in the rabbit aorta, inhibition of neuronal uptake is an insufficient explanation of the potentiating effect of cocaine on maximal responses and, furthermore, support the suggestion that cocaine has a postsynaptic action in this tissue.