Precipitated diazepam withdrawal elevates noradrenergic metabolism in primate brain

Grant, Steven; Galloway, Matthew P.; Mayor, Rowland B.; Fenerty, Joseph P.; Finkelstein, Macie F.; Roth, Robert H.; Redmond, D. Eugene

doi:10.1016/0014-2999(85)90050-0

Cited by 32 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth noting that an increase in basal NE neurotransmission, similar to that reported here, has also been associated with the behavioral depression that occurs following uncontrollable stress (Weiss 1991), as well as following withdrawal from opiates and benzodiazepines (Grant et al 1985;Redmond and Huang 1982;Redmond and Krystal 1984). For example, the stress-induced depression produced by exposure to uncontrollable stress is associated with a transient depletion of NE content in the hypothalamus and the locus coeruleus, and like that of opiate withdrawal, is apparently due to increased NE release and turnover in NE terminal regions (Weiss et al 1980;Weiss and Simson 1986;see Zacharko and Anisman 1989).…”

Section: Discussionsupporting

confidence: 78%

Time-Dependent Effects of Repeated Amphetamine Treatment on Norepinephrine in the Hypothalamus and Hippocampus Assessed with In Vivo Microdialysis

Camp

DeJonghe

Robinson

1997

Neuropsychopharmacology

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 78%

Time-Dependent Effects of Repeated Amphetamine Treatment on Norepinephrine in the Hypothalamus and Hippocampus Assessed with In Vivo Microdialysis

Camp

DeJonghe

Robinson

1997

Neuropsychopharmacology

View full text Add to dashboard Cite

“…Signs and symptoms suggestive of BZD withdrawal can be observed after acute administration of flumazenil to a variety of animal species following repeated exposure to BZD (e.g. Cumin et al, 1982;Lukas and Griffiths, 1982;Grant et al, 1985;Sloan et al, 1991). However, extrapolation of these results to a clinical setting is complicated by the common practice of maximizing the experimental effects by using the highest possible dose of both BZD agonists and antagonists (e.g.…”

Section: Introductionmentioning

confidence: 98%

Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users

1998

View full text Add to dashboard Cite

The acute effects of flumazenil, a benzodiazepine (BZD) receptor antagonist in long-term BZD users were used as a possible test to detect physiological dependence. Thirty-four subjects (20 females, 14 males) aged 26-48 years (mean + SD, 42.4+/-8.5 years), all chronic users of low doses of diazepam (5-20 mg/day, 14.2+/-4.8 mg/day) for 5 to 28 years (10.5+/-6 years), received a single 1-mg i.v. flumazenil dose or saline, infused slowly under double-blind conditions. Physiological dependence was suggested as all patients receiving flumazenil developed an anxiety reaction while the placebo group did not. Flumazenil triggered a qualitatively different reaction amounting to a panic attack during infusion in nine out of 15 patients. These patients had a diagnosis of panic disorder or a history of panic attacks. Caution should be exercised when giving flumazenil to panic patients who are taking BZDs as maintenance treatment.

show abstract

“…In humans, chronic stress and anxiety or panic disorder are associated with hyperactivation of the HPA axis [146,167], In rats, adminis tration of CRH is associated with 'anxious' behavior opposite to that observed in rats treated with benzodiazepines [146], Withdrawal Difficulties (Rebound Insom nia and Anxiety). The role of the noradrener gic system in production of a full withdrawal syndrome after long-term use of benzodiaze pines has been well established in many stud ies [113,114,116,117,119,121,122,124], Also, drugs with a strong direct effect on LC-NE activity have a higher potential for toler ance and withdrawal effects [168]. For exam ple, antihypertensive medication with direct effects on the NE system such as clonidine or methyldopa, may, when abruptly withdrawn, cause rebound hypertension and adrenergic hyperactivity [169], Also, cb-adrenoreceptors and NE significantly modulate limbic sei zures.…”

Section: Tolerance Daytime Anxiety and Other Hy Perexcitability Phenmentioning

confidence: 99%

Benzodiazepine Side Effects: Role of Pharmacokinetics and Pharmacodynamics

Vgontzas

Kales

Bixler³

1995

Pharmacology

103

View full text Add to dashboard Cite

Benzodiazepines have a wide variety of indications. However, CNS and psychiatric adverse reactions, tolerance, and withdrawal effects of benzodiazepines are becoming increasingly recognized and must be better understood for proper drug use. Certain benzodiazepines are associated with memory impairment and other cognitive defects and hyperexcitability phenomena during treatment (early-morning insomnia, daytime anxiety) and following withdrawal (rebound insomnia and anxiety, seizures). Elimination half-life, receptor-binding affinity, effects on the locus coeruleus-norepinephrine (LC-NE) and hypothalamic-pituitary-adrenal (HPA) axes, and the interaction of these factors appear to be major determinants of frequency and severity of these untoward effects. Rapid drug elimination and high receptor-binding affinity were initially suggested as primary underlying factors which determine frequency, severity, and type of the side effects of benzodiazepines during administration and withdrawal. Newer data and information on triazolobenzodiazepines indicate that these psychiatric adverse reactions also relate to whether the benzodiazepine has strong direct effects on the LC-NE and HPA systems. Initial suppression of the LC-NE and HPA systems is followed, on an interdose basis, by a significant rebound and activation. This repetitive pattern of suppression followed by rebound results in a neurophysiologic and behavioral sensitization (kindling) of the limbic system and consequently contributes to central nervous system and psychiatric adverse reactions. The tendency of certain of these side effects to worsen over time supports empirically this neurophysiologic and biochemical model.

show abstract

Precipitated diazepam withdrawal elevates noradrenergic metabolism in primate brain

Cited by 32 publications

References 24 publications

Time-Dependent Effects of Repeated Amphetamine Treatment on Norepinephrine in the Hypothalamus and Hippocampus Assessed with In Vivo Microdialysis

Time-Dependent Effects of Repeated Amphetamine Treatment on Norepinephrine in the Hypothalamus and Hippocampus Assessed with In Vivo Microdialysis

Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users

Benzodiazepine Side Effects: Role of Pharmacokinetics and Pharmacodynamics

Contact Info

Product

Resources

About