The Pharmacological Basis of Therapeutics

Goodman, Louis S.; Gilman, Alfred G.

doi:10.1097/00000446-194109000-00048

Cited by 176 publications

(199 citation statements)

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“…Consequently, a larger dose is required to produce a comparable serum level of NTX to that seen when lower doses are given via nonoral routes. In rats, NTX has an oral bioavailability of 1%, which is lower than the 15 to 25% bioavailability found in humans (Goodman and Gilman, ). This low oral potency of NTX in rats is due to a rapid first pass metabolism, rather than to gastro intestinal factors (Shepard et al., ).…”

Section: Discussionmentioning

confidence: 84%

“…This low oral potency of NTX in rats is due to a rapid first pass metabolism, rather than to gastro intestinal factors (Shepard et al., ). In contrast, VAR is well absorbed after oral administration and has a bioavailability of >87% (Goodman and Gilman, ; Obach et al., ). Therefore, a given dose of VAR is equally effective if given via nonoral or oral routes (McKee et al., ; Steensland et al., ).…”

Section: Discussionmentioning

confidence: 99%

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Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism

Froehlich

Fischer

Dilley

et al. 2016

Alcoholism Clin & Exp Res

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Background This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol experienced P rats that had been drinking alcohol (15% v/v) for 2 hrs/day for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0 or 2.0 mg/kg BW), NTX alone (10.0, 15.0 or 20.0 mg/kg BW) or VAR + NTX in one of four dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side-effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism

Froehlich

Fischer

Dilley

et al. 2016

Alcoholism Clin & Exp Res

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“…Tetracycline drugs have several functional groups with high affinity for ionic binding. Hydrophilic tetracyclines, such as OTC, exhibit a greater ability for complex formation when associated with cations, as opposed to lipophilic derivatives (Goodman & Gilman 1985; Lunestad & Goksoyr 1990). Divalent cations mediate the binding of OTC to macromolecules, which also has a pronounced effect on reducing the antibacterial activity of several drugs including OTC (Lunestad & Samuelsen 2001).…”

Section: Plasma (μG Ml−1) Concentration Of Oxytetracycline In Sea Basmentioning

confidence: 99%

Bioavailability of oxytetracycline in sea bass, Dicentrarchus labrax (L.)

Rigos

Nengas

Alexis

et al. 2004

Journal of Fish Diseases

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“…Several hypotheses have been proposed in an effort to explain how these drugs work: reduction in plasma renin activity, blockade of presynaptic β‐adrenoceptors, reduction in cardiac output or CNS effects. However, there are exceptions to all of these explanations, and none of them can account for their delayed onset (Goodman et al. , 2006).…”

Section: Introductionmentioning

confidence: 99%

The quantal secretion of catecholamines is impaired by the accumulation of β‐adrenoceptor antagonists into chromaffin cell vesicles

Montesinos

Camacho

Machado

et al. 2010

British J Pharmacology

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Background and purpose: The delayed onset of certain effects of antagonists of b-adrenoceptors (b-blockers), such as lowering arterial blood pressure (several days), cannot be explained solely by their effects on b-adrenoceptors, an action that occurs within minutes. Although several mechanisms have been proposed, none of them explain this temporal delay. This work aimed at providing a new explanation based on the interference of these drugs with the functional accumulation of catecholamines within neurosecretory vesicles. Experimental approach: We used the simultaneous on-line monitoring of catecholamine and labetalol release from bovine isolated chromaffin cells and from rat perfused adrenal glands, as well as single cell amperometry, intracellular electrochemistry, patch amperometry and HPLC. Key results: Using amperometry, three b-blockers, labetalol, atenolol and propranolol, reduced the quantal size of secretory events in chromaffin cells, accompanied by a slowing down of exocytosis. By patch amperometry, we found that treatment with b-blockers also increases the chromaffin vesicle volume, thereby creating a functional dilution of catecholamines. Experiments with intracellular electrochemistry show that vesicles cannot uptake new catecholamines. There was progressive accumulation of labetalol in secretory vesicles of bovine adrenal chromaffin cells, and this b-blocker was co-released with catecholamines from rat and bovine chromaffin tissues. Conclusions and implications:We propose that b-blockers are progressively concentrated into sympathetic secretory vesicles, and interfere with the storage of catecholamines and are co-released with the natural transmitters, resulting in a decrease in the sympathetic tone. This could explain the delayed onset of the hypotensive effects of b-blockers. (2010) Keywords: amperometry; chromaffin cells; patch amperometry; secretion; catecholamines; b-adrenoceptor; labetalol; propranolol; atenolol Abbreviations: b-blocker, b-adrenoceptor antagonist; CgB, chromogranin B; DMPP, dimethylphenyl piperazinium; Imax, maximal intensity of amperometrical spikes; m, ascending slope of spikes; Q, spike charge; t1/2, spike width at a half height British Journal of Pharmacology

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The Pharmacological Basis of Therapeutics

Cited by 176 publications

References 0 publications

Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism

Combining Varenicline (Chantix) with Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in a Rodent Model of Alcoholism

Bioavailability of oxytetracycline in sea bass, Dicentrarchus labrax (L.)

The quantal secretion of catecholamines is impaired by the accumulation of β‐adrenoceptor antagonists into chromaffin cell vesicles

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