Effects of Nicergoline on the Cardiovascular System of Dogs and Rats

Huchet, Anne Marie; P, Mouille; Chelly, Jacques E.; Lucet, Bernadette; Doursout, Marie–Françoise; Lechat, Philippe; Schmitt, Henri

doi:10.1097/00005344-198107000-00003

Cited by 24 publications

(4 citation statements)

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“…The inhibitory effect of the potent cx,-adrenoceptor antagonist nicergoline, (Huchet et al, 1981) on the amplitude of myometrial contraction in the PEprimed rat was more pronounced than that observed without prior exposure of the uterus to the a-receptor stimulant (see Figure 1 and Table 1). The excitatory effect of PE on the myometrium and the subsequent relaxation induced by NI further support the involvement of a,-adrenoceptors in the mechanism of uterine contraction (Ishikawa & Fuchs, 1978;Exton, 1981).…”

Section: Discussionmentioning

confidence: 91%

Involvement of α‐adrenoceptors in myometrial responses in the pro‐oestral rat

Acritopoulou-Fourcroy

Marcais-Collado

1988

British J Pharmacology

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Myometrial responses to different agents acting on adrenoceptors were examined in vivo in the pro‐oestrous rat. Changes in spontaneous uterine mechanical activity were recorded isometrically and evaluated in terms of amplitude and duration of uterine contractions. Phenylephrine (10 μg kg−1) markedly increased the amplitude and duration of contractions and 40 μg kg−1 gave rise to tetanic contractions. Administration of either nicergoline (400 μg kg−1) or phentolamine (1000 μg kg−1) to phenylephrine‐primed rat uterus reduced the strength of contractions and phentolamine abolished the phenylephrine‐induced uterine contracture. Following blockade of α2‐adrenoceptors by yohimbine (1000 μg kg−1) and β‐adrenoceptors by propranolol (2400 μg kg−1), a single injection of phenylephrine (100 μg kg−1) increased the amplitude of uterine contractions by 30%. Noradrenaline reduced the amplitude of contractions and caused elevation of the baseline level. The response of myometrium to the combination of both propranolol and noradrenaline was the establishment of uterine contracture with subsequent increase of the duration of contractions. These results clearly demonstrate the involvement of α‐adrenoceptors in the myometrial activity of the rat in vivo during pro‐oestrus.

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Section: Discussionmentioning

confidence: 91%

Involvement of α‐adrenoceptors in myometrial responses in the pro‐oestral rat

Acritopoulou-Fourcroy

Marcais-Collado

1988

British J Pharmacology

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“…We have explored this possibility by studying the effects of nicergoline on human platelets. Nicergoline has been described as a more selective alpha l-adrenergic antagonist, when studied on the cardiovascular system of rats and dogs [25] and on central adrenergic receptors in rats [26]. Nicergoline inhibits the potentiating effect of adrenaline on the aggregation and 3H-5HT secretion induced by low concentrations of all aggregating agents tested, with IC50 ranging from 0.1 to 2.5 pM in human cPRP and between 0.1 to 0.8 #M in intact washed human platelets.…”

Section: Discussionmentioning

confidence: 99%

Potentiation by adrenaline of human platelet activation and the inhibition by the alpha-adrenergic antagonist nicergoline of platelet adhesion, secretion and aggregation

Lanza¹,

Cazenave²,

Beretz³

et al. 1986

Agents and Actions

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Adrenaline (1 to 10 microM) can induce the aggregation of human platelets suspended in citrated plasma but does not induce the aggregation of washed human platelets at doses as high as 1 mM, although these platelets respond normally to ADP, PAF-acether, collagen, arachidonic acid, thrombin, the endoperoxide analog U-46619 and the Ca2+ ionophore A23187. Adrenaline (0.5 microM) potentiates the aggregation and secretion induced by all the previous agonists in citrated platelet-rich plasma (cPRP) or in washed platelets. The activation by adrenaline of human platelets is mediated by alpha 2-adrenergic receptors, as demonstrated by inhibition with a series of adrenergic antagonists. The alpha-adrenergic antagonist nicergoline inhibits the activation of human platelets by adrenaline in the following situations: nicergoline inhibits the aggregation and secretion caused by adrenaline in cPRP (IC50 0.22 microM and 0.28 microM respectively); nicergoline inhibits the aggregation and secretion induced by the combination of adrenaline and each aggregating agent listed above in cPRP (IC50 ranging from 0.1 to 2.5 microM) or in washed platelets (IC50 ranging from 0.1 to 0.8 microM); nicergoline inhibits the binding of 3H-yohimbine to washed human platelets (IC50 0.26 microM); the intravenous administration of nicergoline (0.5 mg/kg per day) to patients inhibits significantly the ex vivo response of their platelets to adrenaline in cPRP. High concentrations of nicergoline also inhibit the aggregation and secretion induced by the aggregating agents listed above in cPRP (IC50 range 108 to 670 microM) and in washed platelets (IC50 range 27 to 140 microM) and the adhesion of platelets to collagen-coated surfaces. This latter effect is not mediated through blockade of alpha-adrenoceptors. A possible role of adrenaline in platelet activation in vivo could justify the use of nicergoline (Sermion), an alpha-adrenergic antagonist in combination therapy to prevent arterial thrombosis.

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“…None of these drugs alter BR sensitivity during either activation or deactivation, but only reset BR by shifting the set-point of the reflex horizontally to the left towards lower pressures (Fig. This sympathetic inhibitory effect is specific for a,-adrenoreceptor blocking drugs such as ARC 239 (Mouille et al, 1980), nicergoline (Huchet et al, 1981), and ketanserin (McCall, 1984;McCall and Schuette, 1984). The lack of reflex tachycardia in response to hypotension may be related to an a,-adrenoreceptor blockade-mediated sympathetic inhibitory effect of the facilitatory a-adrenergic mechanism that is responsible for the increase in sympathetic outflow when BR perfusion pressure is reduced (Shebuschi and Zimmerman, 1985).…”

Section: Antihypertensives and Baroreceptor Control Of Hr Bpmentioning

confidence: 99%

“…The lack of reflex tachycardia in response to hypotension may be related to an a,-adrenoreceptor blockade-mediated sympathetic inhibitory effect of the facilitatory a-adrenergic mechanism that is responsible for the increase in sympathetic outflow when BR perfusion pressure is reduced (Shebuschi and Zimmerman, 1985). This sympathetic inhibitory effect is specific for a,-adrenoreceptor blocking drugs such as ARC 239 (Mouille et al, 1980), nicergoline (Huchet et al, 1981), and ketanserin (McCall, 1984;McCall and Schuette, 1984). However, these drugs do not impair the ability of a-adrenoreceptors to be modulated above or below their resting level of excitation by alterations in sympathetic activity during isometric and dynamic exercise and during cold exposure .…”

Section: Antihypertensives and Baroreceptor Control Of Hr Bpmentioning

confidence: 99%

Antihypertensive Drugs and Baroreceptor Reflex Control of Heart Rate and Blood Pressure

Berdeaux

Giudicelli

1988

Fundamemntal Clinical Pharma

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Summary— The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become «reset», with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension‐induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., α1,‐or β‐adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium‐channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set‐point of the BR response curve towards lower pressures, with no change in HR or R‐R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g. after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP. Regarding BR control of blood pressure, only captopril and especially celiprolol (a β1‐adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure.

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Effects of Nicergoline on the Cardiovascular System of Dogs and Rats

Cited by 24 publications

References 0 publications

Involvement of α‐adrenoceptors in myometrial responses in the pro‐oestral rat

Involvement of α‐adrenoceptors in myometrial responses in the pro‐oestral rat

Potentiation by adrenaline of human platelet activation and the inhibition by the alpha-adrenergic antagonist nicergoline of platelet adhesion, secretion and aggregation

Antihypertensive Drugs and Baroreceptor Reflex Control of Heart Rate and Blood Pressure

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