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EFFECTS OF TRICYCLIC ANTIDEPRESSANTS ON UPTAKE AND RELEASE OF 3H‐NORADRENALINE IN ISOLATED GUINEA‐PIG ATRIA
Author(s) -
Story D. F.,
Story M. E.,
McCulloch M. W.,
Hope W.,
Rand M. J.
Publication year - 1974
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1974.tb00564.x
Subject(s) - tricyclic , guinea pig , pharmacology , medicine , chemistry
SUMMARY 1. Desipramine, nortriptyline, amitriptyline, imipramine and cocaine inhibit the uptake of 3 H‐noradrenaline in isolated guinea‐pig atria. The order of potency is as listed; the concentrations producing 50% inhibition are 0.026, 0.036, 0.193, 0.288 and 3.47 μM, respectively. 2. The effects of desipramine and amitriptyline in a range of concentrations (0.01–100 μM) were tested on the resting and stimulation‐induced efflux of radioactivity from isolated guinea‐pig atria in which adrenergic transmitter stores had been labelled with 3 H‐(‐)‐noradrenaline. 3. Stimulation‐induced efflux is slightly enhanced by a low concentration (0.01 μM) of desipramine, but is markedly reduced by concentrations of 30 and 100 μM. With 100 μM, there is a marked increase in resting efflux. 4. Amitriptyline enhances stimulation‐induced efflux to a greater extent than does desipramine, and the maximal effect is produced with a higher concentration (30 μM). With 100 μM, stimulation‐induced efflux is not significantly altered from control and resting efflux is increased, but to a lesser extent than with 100 μM desipramine. 5. It is concluded that desipramine and amitriptyline exert more than one action on adrenergic transmission: in addition to inhibiting neuronal uptake of noradrenaline, they also release noradrenaline, and desipramine interferes with the release of transmitter in response to nerve stimulation.