Cerebrospinal fluid concentrations of propranolol, pindolol and atenolol in man: evidence for central actions of beta‐adrenoceptor antagonists.

Taylor, Elizabeth A.; Jefferson, D; Carroll, John D.; Turner, Paul

doi:10.1111/j.1365-2125.1981.tb01264.x

Cited by 60 publications

(17 citation statements)

References 20 publications

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“…The greater eNS concentrations off at-soluble ,8-adrenoceptor antagonists are due to greater distribution into the bulk phase of fatty tissue, of which there is a great deal (particularly within non-neuronal glial elements) in the brain, and do not necessarily imply higher drug concentrations at ,8-receptors. While distribution of watersoluble agents into the eNS is slower than for lipidsoluble compounds (Taylor et al 1981), distribution equilibrium eventually occurs and can result 307 in appreciable eNS concentrations. Clinical trials suggest that water-and lipid-soluble agents may have a similar likelihood of altering cerebral function (Gengo et al 1987;Salem & McDevitt 1983).…”

Section: Distributionmentioning

confidence: 99%

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

Nattel

Gagne

Pineau

1987

Clinical Pharmacokinetics

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Lignocaine (lidocaine) and beta-adrenoceptor antagonists are widely used after acute myocardial infarction. The therapeutic value of these agents depends on the achievement and maintenance of safe and effective plasma concentrations. Lignocaine pharmacokinetics after acute myocardial infarction (MI) are controlled by a number of variables. The single most important is left ventricular function, which affects both volume of distribution and plasma clearance. Other major factors include bodyweight, age, hepatic function, the presence of obesity, and concomitant drug therapy. Lignocaine is extensively bound to alpha 1-acid glycoprotein, a plasma protein which is also an acute phase reactant. Increases in alpha 1-acid glycoprotein concentration occur after an acute MI, decreasing the free fraction of lignocaine in the plasma and consequently decreasing total plasma lignocaine clearance without altering the clearance of non-protein-bound lignocaine. Complex changes in lignocaine disposition occur with long term infusions, and therefore early discontinuation of lignocaine infusions (within 24 hours) should be undertaken whenever possible. Because the risk of ventricular tachyarrhythmia declines rapidly after the onset of an acute MI, lignocaine therapy can be rationally discontinued within 24 hours in most patients. Lignocaine has a narrow toxic/therapeutic index, so that pharmacokinetic factors are critical in dose selection. In contrast, beta-adrenoceptor antagonists' adverse effects are more related to the presence of predisposing conditions (such as asthma, heart failure, bradyarrhythmias, etc.) than to plasma concentration. The pharmacokinetics of beta-adrenoceptor antagonists are important to help assure therapeutic efficacy, to provide information about the anticipated time course of drug action, and to predict the possible role of ancillary drug effects (such as direct membrane action) and loss of cardioselectivity. Lipid solubility is the main determinant of the pharmacokinetic properties of a beta-adrenoceptor antagonist. Lipid-soluble agents like propranolol and metoprolol are well absorbed orally, and undergo rapid hepatic metabolism, with important presystemic clearance and a short plasma half-life. Water-soluble drugs like sotalol, atenolol, and nadolol are less well absorbed, and are eliminated more slowly by renal excretion. Clinical assessment of beta-adrenoceptor antagonism is more valuable than plasma concentration determinations in evaluating the adequacy of the dose of a particular beta-adrenoceptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Distributionmentioning

confidence: 99%

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

Nattel

Gagne

Pineau

1987

Clinical Pharmacokinetics

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“…The latter drug has also found a clinical use in the treatment of migraine (Anthony, 1978;Weber & Reinmuth, 1972) and anxiety states (Heiser & DeFrancisco, 1976;Linken, 1971 (Young et al, 1975;Taylor et al, 1981;Kuroda et al, 1988) an interference with 5-HT systems may be important (Hallberg, 1987).…”

Section: Introductionmentioning

confidence: 99%

Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration

Málly

Connick

Stone

1991

British J Pharmacology

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The mouse neocortical slice has been used to examine the sensitivity of neurones to isoprenaline, 5‐hydroxytryptamine (5‐HT) and adenosine acutely and following chronic treatment of animals with propranolol or theophylline. While having little effect alone, all three agonists enhanced the d.c. depolarizing potential produced by N‐methyl‐d‐aspartate (NMDA). The effect of (−)‐isoprenaline (0.2 μm) was shared by (+)‐isoprenaline at the much higher concentration of 10 μm. Superfusion of slices with theophylline or 8‐phenyltheophylline blocked responses to adenosine with evidence of selectivity. A single injection of theophylline 24 h before slice preparation did not alter agonist sensitivity, but when administered daily at 100 mg kg−1 for 14 days, the xanthine caused a loss of sensitivity to adenosine and (−)‐isoprenaline but not 5‐HT. The lower dose of theophylline, 10 mg kg−1 daily, also led to a loss of adenosine responses but no change of sensitivity to the amines. Following the 14 day treatment with theophylline at 100 mg kg−1 daily in two groups of mice, responses to adenosine recovered to control levels after 20 days. Propranolol superfusion blocked responses to both isomers of isoprenaline and 5‐HT but did not affect sensitivity to adenosine. Chronic treatment with propranolol at 25 mg kg−1 daily for 14 days induced a loss of sensitivity to (−)‐isoprenaline and 5‐HT but not adenosine. A lower dose of 5 mg kg−1 daily caused no change in responses to adenosine or 5‐HT, but yielded an increased sensitivity to (−)‐isoprenaline. The results are discussed with respect to reports of receptor up‐regulation in binding studies; caution is clearly required in extrapolating from such work to receptor activity in a functional system, especially in the case of theophylline and adenosine.

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“…Beta blockers might exert an effect in the centrai nervous system (CNS), because betaadrenergic receptors can be found in the human cortex 1141, and propranolol, pindolol, and atenolol have been shown to cross the blood-brain barrier [15].…”

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confidence: 99%

Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials

Diener

Scholz

Dichgans

et al. 1989

Annals of Neurology

113

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The present study used recordings of visual potentials evoked by pattern reversal (VEPs) to investigate the central effects of three drugs used in migraine prophylaxis: the calcium channel blocker nifedipine, the beta-1-selective blocker metoprolol, and the nonselective beta adrenoreceptor blocker propranolol. The study involved 58 patients with common or classical migraine who were treated in a double-blind randomized study over a period of 7 months, while the effectiveness of prophylactic treatment was recorded in headache diaries that were subjected to time series analysis. VEPs were recorded at the beginning of a 2-month baseline period without treatment, after 4 months of treatment, and at the end of a 3-month washout period. At baseline, migraine patients had significantly higher VEP amplitudes and longer latencies than did a group of 87 healthy control subjects. Patients were separated by statistical analysis into responders and nonresponders to each prophylactic treatment. Nifedipine had no effects on the frequency, intensity, and duration of migraine attacks, nor on amplitude and latency of the VEPs. In contrast, the use of beta blockers resulted in a significant decrease in VEP amplitude, both in responders and nonresponders, whereas VEP latency remained unchanged. VEP amplitudes returned to the initial values at follow-up in the nonresponders, but stayed at lower levels in responders. Beta blockers thus appear to have a significant effect on the increased excitability of the visual system in patients with migraine, although their action is not directly related to their reduction of migraine frequency.

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Cerebrospinal fluid concentrations of propranolol, pindolol and atenolol in man: evidence for central actions of beta‐adrenoceptor antagonists.

Cited by 60 publications

References 20 publications

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration

Central effects of drugs used in migraine prophylaxis evaluated by visual evoked potentials

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