Ketanserin and α1-Adrenergic Antagonism in Humans

Zabludowski, J. R.; Ball, Stephen G.; Robertson, J. I. S.

doi:10.1097/00005344-198500077-00036

Cited by 15 publications

(7 citation statements)

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“…Furthermore, whereas heart rate is usually unchanged during longterm prazosin therapy (Lund-Johansen, 1974), in this and other studies heart rate was significantly reduced with ketanserin (Fagard et al, 1985;Persson etal., 1983). A previous study, which demonstrated weak a-adrenoceptor blocking activity in normotensive subjects, found no reduction in blood pressure (Zabludowski et al, 1985) and the evidence of only modest aadrenoceptor antagonist activity in this study also suggests that this mechanism is unlikely to account entirely for the antihypertensive effect. There is some dispute about the extent of the reduction in peripheral vascular resistance associated with the antihypertensive effect of ketanserin (Fagard et al, 1984;Omvik & Lund-Johansen, 1983) and in this study ketanserin had no effect on the pressor responses to angiotensin II.…”

Section: Discussioncontrasting

confidence: 53%

Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics.

Donnelly¹,

Elliott²,

Modesti³

et al. 1987

Brit J Clinical Pharma

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1 In nine patients with essential hypertension, following single and multiple doses of ketanserin, assessments were made of blood pressure and heart rate, QT interval, and pressor responses to phenylephrine and angiotensin II. 2 Significant reductions in blood pressure occurred for 6 h after the first dose, on average 23/14 mm Hg supine, and there was a comparable antihypertensive effect after 1 month's treatment.3 There were small but significant rightward shifts (1.5 to 2-fold) in the phenylephrine pressor-response curves but no changes in the responsiveness to angiotensin II. 4 The QT interval (QTJ) was significantly increased after 1 month's treatment: at 1 h after dosing 334 ± 32 ms after 1 month of ketanserin compared with 302 ± 31 ms after placebo. 5 The elimination half-life and AUC for ketanserin were both significantly increased at steady state compared with the first dose: respectively 13.4 vs 4.3 h for half-life and 830 vs 437 ng ml-1 h for AUC. 6 Ketanserin had no significant effects on baroreflex function, plasma renin activity, aldosterone, catecholamines and 24 h urinary excretion.

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Section: Discussioncontrasting

confidence: 53%

Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics.

Donnelly¹,

Elliott²,

Modesti³

et al. 1987

Brit J Clinical Pharma

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“…1983; 28753, Correspondence). With chronic treatment (or prolonged infusion), or with high intravenous doses, ketanserin (unlike the al-antagonist prazosin) causes a nonparallel rightward shift in dose-response curves to methoxamine and norepinephrine in hypertensive patients (18)(19)(20). This could be due to aladrenergic blockade but also to an altered wall-to-lumen ratio following reduction in blood pressure by other mechanisms (20).…”

Section: Discussionmentioning

confidence: 99%

“…With chronic treatment (or prolonged infusion), or with high intravenous doses, ketanserin (unlike the al-antagonist prazosin) causes a nonparallel rightward shift in dose-response curves to methoxamine and norepinephrine in hypertensive patients (18)(19)(20). This could be due to aladrenergic blockade but also to an altered wall-to-lumen ratio following reduction in blood pressure by other mechanisms (20). By contrast, during acute administration of ketanserin at lower doses, al-blockade does not appear to contribute to the acute antihypertensive effect of ketanserin (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Beneficial hemodynamic effects of ketanserin in patients with cirrhosis: Possible role of serotonergic mechanisms in portal hypertension

et al. 1987

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We studied the acute effects of ketanserin, a serotonin S2 antagonist, on systemic and splanchnic hemodynamics in 11 patients with cirrhosis. Mean arterial pressure decreased moderately but significantly after ketanserin. This effect was maximal at 5 min and correlated to the severity of cirrhosis. Cardiac index and systemic vascular resistance were not significantly changed. The hepatic venous pressure gradient, used as an index of portal pressure, significantly decreased after ketanserin (-23%). Azygos blood flow, a reflection of superior portosystemic collateral blood flow, also significantly decreased (-26%), but this effect was delayed, progressive and not correlated to the arterial pressure decrease. Hepatic blood flow was unchanged. These findings suggest that the systemic and splanchnic circulations may be hypersensitive to ketanserin in cirrhotic patients, and that serotonergic mechanisms may contribute to maintain portal hypertension. New specific antiserotonergic drugs deserve further evaluation for potential therapeutic implications in portal hypertension.

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“…In several studies it has been suggested that the antihypertensive activity ofketanserin may be attributed to the al-adrenergic receptor blocking properties of the compound [37,38] or to a centrally mediated inhibition of sympathetic vascular tone [39,40]. Although the involvement of al-adrenergic receptor blockade cannot be excluded, it is rather unlikely that this is the sole mechanism involved, because ketanserin also lowers arterial blood pressure in patients with complete autonomic insufficiency [41].…”

Section: The Interaction Between Al-adrenergic and S2-serotonergic Rementioning

confidence: 99%

Serotonin and acute cardiovascular disorders

Reneman

Starre

1990

Cardiovasc Drug Ther

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In this survey the possible role of serotonin in such acute disorders as systemic and pulmonary hypertension following cardiac surgery is discussed. Although platelets are activated during cardiopulmonary bypass, the increase in serotonin plasma levels is limited because the serotonin released is taken up by normal platelets and endothelial cells. This does not imply that serotonin is not involved in the origin of systemic hypertension during and after cardiac surgery, because subthreshold or threshold doses of this amine amplify the vasoconstrictive effect of, for example, epinephrine and norepinephrine, the levels of which are significantly elevated under these circumstances. That serotonin plays a role through its amplifying effect is supported by the finding that ketanserin, a specific S2-serotonergic receptor antagonist with alpha 1-adrenergic receptor blocking properties, effectively lowers arterial blood pressure in patients with systemic postoperative hypertension by combined blockade of these receptors. The compound is also effective in the treatment of pulmonary hypertension after valve replacement, indicating that serotonin plays a role in the origin of this disorder. This idea is supported by the experimental finding that serotonin induces pulmonary hypertension. It is an interesting observation that, unlike such compounds as nitroprusside, ketanserin does not affect intrapulmonary shunting in patients with systemic hypertension and even reduces the intrapulmonary shunt fraction in patients with pulmonary hypertension. These findings indicate that this compound dilates the resistance vessels in well-ventilated, but not in poorly ventilated areas, and may dilate constricted bronchi.(ABSTRACT TRUNCATED AT 250 WORDS)

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Ketanserin and α1-Adrenergic Antagonism in Humans

Cited by 15 publications

References 0 publications

Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics.

Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics.

Beneficial hemodynamic effects of ketanserin in patients with cirrhosis: Possible role of serotonergic mechanisms in portal hypertension

Serotonin and acute cardiovascular disorders

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