Metabolites of Pindolol in Different Animal Species

Kiechel, J. R.; Niklaus, P.; Schreier, E.; Wagner, H. H.

doi:10.3109/00498257509060375

Cited by 21 publications

(7 citation statements)

References 11 publications

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“…For instance in the rat, the biological half-life for the disappearance of pindolol from plasma, following oral or intravenous administration, is reported to be approximately 30 min (Pacha, 1969). Moreover in rats, pindolol is extensively metabolized, the metabolites arising principally from side-chain conjugation with glucuronic acid, hydroxylation or oxidation and conjugation of the indole ring, and oxidative ring scission (Kiechel et al, 1975). In contrast, the biological half-life of pindolol in human plasma, following oral administration, is reported to be approximately 3 h (Pacha, 1969).…”

Section: Discussionmentioning

confidence: 99%

Studies on the Cardiovascular Effects of Pindolol in Doca/Saline Hypertensive Rats

Buckinghamm

Hamilton

Robson

1977

British J Pharmacology

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1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS‐rats) is described. In DS‐rats, pindolol (10‐50 μg/kg) produced a dose‐dependent fall in blood pressure and elevation of resting heart rate. 2 The hypotensive response and tachycardia produced by oral pindolol (50 μg/kg) in DS‐rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by β‐adrenoceptor stimulation. 3 After mecamylamine (10 mg/kg), oral pindolol (50 μg/kg) produced a further fall in blood pressure in DS‐rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature. 4 Pretreatment with oral pindolol (10 or 50 μg/kg) resulted in a reduction of neuronally‐induced tachycardia in pithed DS‐rats; neuronally‐evoked pressor effects were also antagonized by pindolol (50 μg/kg, orally). 5 Whereas pindolol, 50 μg/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS‐rats the same dose intravenously produced a smaller response of delayed onset (80 minutes). 6 In anaesthetized DS‐rats, an equivalent degree of cardiac β‐adrenoceptor blockade was produced by pretreatment with pindolol, 50 μg/kg orally (2 h previously) or intravenously (1 h previously). 7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS‐rats, the tachycardia produced by intravenous isoprenaline, 3 μg/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes). 8 The hypotensive response and tachycardia produced by oral pindolol, 50 μg/kg, in DS‐rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525‐A), 80 mg/kg. 9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS‐rat are mediated by a metabolite(s) acting by stimulation of peripheral β‐adrenoceptors.

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Section: Discussionmentioning

confidence: 99%

Studies on the Cardiovascular Effects of Pindolol in Doca/Saline Hypertensive Rats

Buckinghamm

Hamilton

Robson

1977

British J Pharmacology

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“…In all the studies the drug was determined in plasma and urine by a fluorimetric method (Pacha, 1969). This method proved to be sensitive and specific for the unchanged drug, because the polar metabolites (Kiechel, Niklaus, Schreier & Wagner, 1975) were eliminated by the extraction procedure. The volunteers participating in the studies A to E were all different, except for the six in studies Al and A2 who received the drug orally and intravenously.…”

Section: Pindolol Ap-adrenoceptor Blocking Agent With a Negligible Fmentioning

confidence: 99%

Pindolol, a beta‐adrenoceptor blocking agent with a negligible first‐ pass effect.

Meier¹,

Nüesch²

1977

Brit J Clinical Pharma

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“…The OH CH 3 isopropylaminopropoxy side-chain in pamatolol is metabolically altered in consecutive steps to a lactic acid derivative, which has been found in the urine in different species. From a quantitative point of view,this metabolic route is of minor importance for pamatolol but it is commonly reported for most beta-adrenoceptor antagonists (9)(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Hoffmann¹,

Skånberg²,

Borg³

1979

European Journal of Drug Metabolism and Pharmacokinetics

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The metabolism of pamatolol was studied in man, dogs, rats and mice after oral administration of a single dose. The drug was well absorbed in the gastro-intestinal tract and excreted in the urine, mainly in unchanged form, within 24 hrs. Four urinary metabolites were identified by gas chromatographic-mass spectrometric techniques. The metabolic data, in man, dog and mouse was found to be similar, both qualitatively and quantitatively. One metabolism route, involving aliphatic hydroxylation and subsequent oxidation, was found, to a significant extent only in the rat. The species variation between the mouse and the rat with regard to long-term toxicity of pamatolol is discussed. Artefact formation during trace analysis was observed.

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Metabolites of Pindolol in Different Animal Species

Cited by 21 publications

References 11 publications

Studies on the Cardiovascular Effects of Pindolol in Doca/Saline Hypertensive Rats

Studies on the Cardiovascular Effects of Pindolol in Doca/Saline Hypertensive Rats

Pindolol, a beta‐adrenoceptor blocking agent with a negligible first‐ pass effect.

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

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