Modification by a tricyclic series of compounds of the noradrenaline effect on the cat nictitating membrane

I The effect of a series of antidepressant drugs on noradrenaline accumulation was studied in the isolated anococcygeus muscle of the rat. 2 The most potent inhibitors of noradrenaline accumulation were nortriptyline, desipramine and protriptyline. Opipramol, trimipramine and iprindole were active only in high concentrations. 3 Contractions of the anococcygeus muscle produced by noradrenaline were strongly potentiated by nortriptyline, desipramine and protriptyline. Other uptake inhibitors were less active in potentiating the noradrenaline response. 4 Nortriptyline, in concentrations that potentiated the action of noradrenaline, reduced or abolished the response to tyramine.

Section: Discussionmentioning

confidence: 93%

Effects of Antidepressant Drugs on Noradrenaline Accumulation and Contractile Responses in the Rat Anococcygeus Muscle

Doggrell

Woodruff

1977

“…Although potentiation of the response to NA could sometimes be observed when the response to tyramine was antagonized, on many occasions no potentiation of the response to NA could be seen (see Figures 3 and 4). This observation may reflect the postsynaptic adrenoceptor blocking properties of desipramine (see Sturman, 1970;McCulloch & Story, 1972;Bradshaw et al, 1971;1974). It is possible that, in some experiments, the blockade of postsynaptic receptors by desipramine prevented the development of the potentiation of responses to NA which would have resulted from the presynaptic uptake blockade.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that the tricyclic antidepressant drug, desipramine, blocks the uptake of tyramine into sympathetically innervated tissues (Brodie, Costa, Groppetti & Matsumoto, 1970) and thus antagonizes pharmacological responses to tyramine (Gessa, Vargin & Crabai, 1966;Fozard & Mwaluko, 1976). However, desipramine can also block the uptake of NA (Hertting, Axelrod & Whitby, 1961;Iversen, 1965) which may result in potentiation of the responses to NA (Sigg, Soffer & Gyermek, 1963;Sturman, 1970;McCulloch & Story, 1972). Thus desipramine and other uptake-blocking tricyclic antidepressants (e.g.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Responses of Single Cortical Neurones to Tyramine and Noradrenaline: Effects of Desipramine

Bevan

Pun

Szabadi

1978

1 The technique of microelectrophoresis was used in order to compare the actions of tyramine and noradrenaline on single neurones in the cerebral cortex of the rat. 2 Tyramine could both excite and depress cortical neurones. Each tyramine-sensitive cell was also sensitive to noradrenaline. There was a high correlation between the directions of responses to tyramine and noradrenaline, most cells excited by tyramine being excited by noradrenaline, and most cells depressed by tyramine being depressed by noradrenaline. 3 In the case of both excitatory and depressant responses, tyramine appeared to be less potent than noradrenaline. 4 Tyramine evoked 'slower' responses than noradrenaline, both the latencies to onset and the recovery times being longer for responses to tyramine than for responses to noradrenaline. 5 When the rates of release of tyramine and noradrenaline from micropipettes were measured in vitro, no significant difference could be observed between the transport numbers of the two drugs. Thus the difference in potency between the two drugs, and the difference in the time courses of responses to the two drugs, are presumably of biological origin. 6 Desipramine could discriminate between neuronal responses to tyramine and noradrenaline: responses to tyramine were antagonized, while responses to noradrenaline were either potentiated or unaffected. Responses to DL-homocysteic acid were not affected by desipramine. 7 The results are consistent with the hypothesis that tyramine is an indirectly acting sympathomimetic amine in the brain, and desipramine acts by blocking the uptake of both tyramine and noradrenaline into presynaptic noradrenergic nerve terminals.

“…The antagonism of the responses may be due to a post-synaptic receptor blocking action of the antidepressants. There is experimental evidence that imipramine and desipramine block peripheral o!-adrenoceptors (Callingham, 1966;Sturman, 1970;McCulloch & Story, 1972), and also have an anti-5-HT activity in peripheral smooth muscle systems (Domenjoz & Theobald, 1959). Potentiation of neuronal responses to the monoamines by imipramine and desipramine may reflect the blockade of uptake of NA and 5-HT into pre-synaptic terminals.…”

Section: Effect On Responses To Glutamatementioning

confidence: 99%

“…Tricycic antidepressants block the uptake of NA into sympathetically innervated tissues (Hertting, Axelrod & Whitby, 1961;Iversen, 1965), and they block the uptake of 5-HT into blood platelets (Todrick & Tait, 1969). These drugs are also able to potentiate the responses of adrenergically innervated tissues to exogenously applied NA (Sigg, Soffer & Gyermek, 1963;Sturman, 1970;McCulloch & Story, 1972) and 5-HT (Gyermek & Possemato, 1960;Sigg et al, 1963), and to sympathetic nerve stimulation (Sigg et al, 1963). It has been suggested that the potentiation of responses to NA is due to the blockade of uptake into nerve terminals (Hertting et al, 1961;Iversen, 1965;Schildkraut, 1965).…”

Section: Introductionmentioning

confidence: 99%

Effects of Imipramine and Desipramine on Responses of Single Cortical Neurones to Noradrenaline and 5‐hydroxytryptamine

Bradshaw

Roberts

Szabadi

1974

1 The technique of microelectrophoresis was used in order to study the effects of imipramine and desipramine on single neurones in the somatosensory cortex of the cat, anaesthetized with halothane. 2 Imipramine and desipramine, when applied for a brief period, did not affect the firing rate of the vast majority of the neurones tested. 3 Both potentiation and antagonism of excitatory responses to noradrenaline could be observed after a brief application of either of the antidepressants. Four drug-interaction patterns could be distinguished: potentiation of immediate onset; potentiation reaching its maximum after a delay; antagonism followed by potentiation; antagonism followed by recovery.4 When different doses of the same antidepressant were applied, it was found that the drug-interaction patterns were related to the dose of antidepressant applied, a lower dose causing potentiation, and a higher dose antagonism of the response. 5 Both potentiation and antagonism of depressant responses to noradrenaline could be observed. 6 Both excitatory and depressant responses to 5-hydroxytryptamine were modified by imipramine and desipramine: a smaller dose of the antidepressant potentiated, and a higher dose antagonized the responses. 7 Excitatory responses to glutamate were not affected by imipramine and desipramine.