THE CARDIOVASCULAR EFFECTS OF <scp>l</scp>‐DOPA IN THE PITHED RAT

Edén, Elisabeth; Nasmyth, P. A.

doi:10.1111/j.1476-5381.1974.tb09664.x

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…L-DOPA increased both blood pressure and heart rate in the pithed rat after either intravenous or intraduodenal administration. From the literature, such effects can be suppressed by prior treatment with inhibitors of AADC (Henning & Rubenson, 1970a,b;Eden & Nasmyth, 1974), which implicates dopamine and/or noradrenaline as the agents responsible for the cardiovascular effects. Presumably, these amines either act directly to stimulate cardiovascular adrenoceptors or, in the case of dopamine, in part indirectly by displacing noradrenaline from its stores within peripheral sympathetic nerves (Farmer, 1966;Tsai et al, 1967).…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L‐DOPA without modifying its cardiovascular effects

Fozard¹,

Palfreyman²,

Robin³

et al. 1986

British J Pharmacology

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The potential of a new, potent, irreversible and selective inhibitor of monoamine oxidase type B, (E)‐2‐(3,4‐dimethoxyphenyl)‐3‐fluorallyamine (MDL 72145), to augment the effects of L‐DOPA in an animal model which reproduces the biochemical defect of Parkinson's disease has been evaluated. In rats bearing unilateral 6‐hydroxydopamine lesions of the nigro‐striatal dopamine pathways, both MDL 72145 and clorgyline, a selective inhibitor of MAO A, augmented the contralateral turning response to L‐DOPA combined with carbidopa. The potential of inhibitors of MAO to interact adversely in the periphery with L‐DOPA was investigated in the pithed rat; L‐DOPA was given either intravenously or intraduodenally. Clorgyline consistently potentiated L‐DOPA when given 18 h before testing. Neither MDL 72145 nor the selective inhibitor of MAO B, L‐deprenyl, augmented the cardiovascular effects of intraduodenally administered L‐DOPA. The data provide no reason to suppose that MDL 72145 would be very different in clinical use from L‐deprenyl which is both effective and well‐tolerated as an adjunct to the L‐DOPA‐based therapy of Parkinson's disease.

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Section: Discussionmentioning

confidence: 99%

Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L‐DOPA without modifying its cardiovascular effects

Fozard¹,

Palfreyman²,

Robin³

et al. 1986

British J Pharmacology

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“…That the long exposure to catecholamines of tissues receiving a sympathetic innervation results in a reduced response of those tissues to catecholamines is well established (Blacket, Pickering & Wilson, 1950;Duner & von Euler, 1957;Trendelenburg, 1971;Eden & Nasmyth 1974;Langer & Dubocovich, 1977). The latter authors showed for the first time that presynaptic as well as postsynaptic responses are Table 3 The effect of noradrenaline (NA) and acetylcholine on the tone of the mouse isolated vas deferens before and after perfusing magnesium-free Krebs solution containing noradrenaline (3 x 10-6 M-2 x 10-5 M) through the organ-bath for 30 min; the effects of the addition of cocaine (10-5 M) affected.…”

Section: Discussionmentioning

confidence: 99%

Desensitization by Noradrenaline of Responses to Stimulation of Pre‐ and Postsynaptic Adrenoceptors

Ball

Danks

Dorudi

et al. 1982

British J Pharmacology

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The effect of exposing isolated preparations of rat aortic strip, rat atria and mouse vas deferens to perfusions of Krebs solution containing various concentrations of noradrenaline on their sensitivity to the drug has been determined. The responses evoked by stimulation of postsynaptic adrenoceptors in all the tissues and presynaptic α‐adrenoceptors in the mouse vas deferens were diminished by the perfusion of noradrenaline through the organ bath for 30 min. The concentration of noradrenaline required to produce desensitization was higher in the mouse vas deferens than in the other tissues and more was required to desensitize the chronotropic responses than the inotropic responses in rat isolated atria. The inclusion of cocaine (10−5m) in the bathing solution to block uptake1 increased the sensitivity of most tissues to noradrenaline. With the possible exception of the response to stimulation of presynaptic receptors in the mouse vas deferens, desensitization was somewhat increased in its presence. When uptake2 was blocked by oestradiol (10−5m), it was not possible to desensitize the contractor responses of the aortic strip and vas deferens to exogenous noradrenaline, nor the inotropic response of the atria to the drug. However, oestradiol failed to block the desensitization of chronotropic responses and responses to stimulation of presynaptic receptors in the vas deferens. Blockade of monoamine oxidase (MAO) with iproniazid (7.2 × 10−4m) or with pargyline (5 × 10−4 m) did not affect the desensitization process in the aortic strip. Blockade of catechol‐O‐methyltransferase (COMT) with U‐0521 (5.3 × 10−5m) greatly increased desensitization in the aortic strip and desensitization of inotropic responses in the atria. It had no effect on desensitization of chronotropic responses. Its effect on responses in the mouse vas deferens was not determined. The perfusion of methoxamine at concentrations about 1000 times higher than those of noradrenaline also produced desensitization in the aortic strip. The desensitization of presynaptic receptors in the mouse vas deferens was shown to be specific and that of the responses to postsynaptic receptor stimulation to be non‐specific. It is concluded that responses to adrenoceptor stimulation may be desensitized by accumulation of noradrenaline inside the cells bearing the receptors and that the desensitization is caused by noradrenaline itself not by a metabolite. Desensitization may also be caused without accumulation of noradrenaline in uptake2 and for some receptors these may not be alternative mechanisms.

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PROCEEDINGS OF THE British Pharmacological Society

Chieruttini¹,

Franklin²

1976

British J Pharmacology

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THE CARDIOVASCULAR EFFECTS OF l‐DOPA IN THE PITHED RAT

Cited by 3 publications

References 15 publications

Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L‐DOPA without modifying its cardiovascular effects

Selective inhibition of monoamine oxidase type B by MDL 72145 increases the central effects of L‐DOPA without modifying its cardiovascular effects

Desensitization by Noradrenaline of Responses to Stimulation of Pre‐ and Postsynaptic Adrenoceptors

PROCEEDINGS OF THE British Pharmacological Society

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