Chronopharmacokinetics of beta-receptor blocking drugs of different lipophilicity (propranolol, metoprolol, sotalol, atenolol) in plasma and tissues after single and multiple dosing in the rat

Lemmer, Björn; Winkler, H.; Ohm, Thomas G.; Fink, Manfred

doi:10.1007/bf00586708

Cited by 65 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 h for the racemic drug administered to rats. 16 The fraction of each enantiomer eliminated unmetabolized in rat urine Cf . 1 was calculated using the following equation:…”

Section: (2)mentioning

confidence: 99%

Pharmacokinetics of Atenolol Enantiomers in Humans and Rats

Mehvar

Gross

Kreamer

1990

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…5 h for the racemic drug administered to rats. 16 The fraction of each enantiomer eliminated unmetabolized in rat urine Cf . 1 was calculated using the following equation:…”

Section: (2)mentioning

confidence: 99%

Pharmacokinetics of Atenolol Enantiomers in Humans and Rats

Mehvar

Gross

Kreamer

1990

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…significantly attenuates the stress-induced increase in plasma renin activity [5]. As stated before, propranolol crosses the blood-brain barrier [17,18], Nevertheless, the data with so talol suggest that stress-induced increases in PRA and PRC are influenced by catecholamine receptors which are not antag onized by sotalol and are not likely P-adrenoceptors. These could be other catecholamine receptors, such as a-adrenocep-tors, or receptors for other neuroactive substances.…”

Section: Discussionmentioning

confidence: 66%

“…Since propranolol crosses the blood-brain barrier [17,18], it is possible that it acts at a (1-adrenoceptor located in the PVN. Thus, this (1-receptor could be involved in mediating the effect of stress on renin and corticosterone secretion.…”

mentioning

confidence: 99%

Stress-Induced Renin and Corticosterone Secretion Is Mediated by Catecholaminergic Nerve Terminals in the Hypothalamic Paraventricular Nucleus

et al. 1990

View full text Add to dashboard Cite

Cell bodies in the hypothalamic paraventricular nucleus (PVN) mediate stress-induced increases in renin and corticosterone secretion. Since the PVN has an extensive catecholaminergic innervation, we wanted to determine the role of catecholamines in the neuroendocrine response to stress. The stressor was a conditioned emotional (fear) response paradigm (CER). The catecholamine neurotoxin, 6-hydroxydopamine (6-OHDA), was injected into the PVN 14 days before the rats were subjected to the CER procedure. Damage to noradrenergic nerve terminals was verified immunocytochemically, using an antibody against dopamine β-hydroxylase. Injection of 6-OHDA into the PVN prevented the stress-induced increase in plasma renin activity (PRA), plasma renin concentration (PRC) and plasma corticosterone concentration, suggesting that intact catecholaminergic innervation of neurons in the PVN is necessary for the stress-induced increase in renin and corticosterone secretion. To determine if β-adrenoceptors in the PVN mediate the effect of stress on renin and corticosterone secretion, the β-adrenoceptor antagonist sotalol was injected into the PVN through chronically implanted bilateral cannulae. The injection was performed on the 4th day of the CER paradigm, just before the rats were placed into the CER chamber. Sotalol prevented the stress-induced increase in corticosterone concentration, but did not diminish the stress-induced increase in PRA and PRC. These results suggest that the stress-induced increase in corticosterone concentration is influenced by β-adrenoceptors in the PVN. The stress-induced increase in PRA and PRC is mediated by different receptors whose ligands might be catecholamines acting at non-β-receptors or other neuroactive substances colocalized in catecholaminergic nerve terminals.

show abstract

“…Verapamil also accumulates in the lungs and less in skeletal muscle [Hamann et al 1983;Schwartz et al 1986;Todd and Abernethy 1987]. Atenolol accumulation in the lungs is lower than that of propranolol when administered in an equimolar dose [Lemmer et al 1985;Davies and McAinsh t986]. In view of the fact that an increase in the plasma concentrations of propranotol and verapamil was found, but not of atenolol, competition for receptors with agonists (catecholamines) during exercise is unlikely.…”

Section: Discussionmentioning

confidence: 95%

Exercise and the pharmacokinetics of propranolol, verapamil and atenolol

Baak¹,

Mooij²,

Schiffers³

1992

Eur J Clin Pharmacol

View full text Add to dashboard Cite

The volumes of distribution of the beta-adrenoceptor blocking agents propranolol and atenolol, and the calcium antagonist verapamil, during exercise have been investigated. Changes in the plasma concentrations of atenolol and propranolol during exhaustive exercise at 70% of maximal aerobic power were compared after 1 week of oral treatment (propranolol 80 mg b.d. and atenolol 100 mg once daily) in 12 healthy volunteers. In a second study the effect of 10 min exercise at 50% of maximal aerobic power on steady state plasma concentrations of propranolol, atenolol and verapamil was compared in 7 healthy subjects. The drugs were administered by a continuous intravenous infusion. The plasma concentration of atenolol was not changed by exercise in either study, but the plasma concentrations of propranolol and verapamil were significantly increased in both studies. However, after correction for changes in plasma volume during exercise, the plasma propranolol concentration was not significantly elevated in the second study. From the results it is concluded that exercise led to a reduction in the volume of distribution of propranolol during prolonged exercise (25 min) at 70% Wmax, which was not clearly demonstrable during 10 min exercise at 50% Wmax. The volume of distribution of verapamil was reduced during 10 min exercise at 50% Wmax. No change in the volume of distribution of atenolol during exercise could be shown. The changes in the volumes of distribution of propranolol and verapamil during exercise may contribute to preventing an increase in the half-life of these drugs in patients performing prolonged physical exercise.

show abstract

Chronopharmacokinetics of beta-receptor blocking drugs of different lipophilicity (propranolol, metoprolol, sotalol, atenolol) in plasma and tissues after single and multiple dosing in the rat

Cited by 65 publications

References 29 publications

Pharmacokinetics of Atenolol Enantiomers in Humans and Rats

Pharmacokinetics of Atenolol Enantiomers in Humans and Rats

Stress-Induced Renin and Corticosterone Secretion Is Mediated by Catecholaminergic Nerve Terminals in the Hypothalamic Paraventricular Nucleus

Exercise and the pharmacokinetics of propranolol, verapamil and atenolol

Contact Info

Product

Resources

About