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Biomedical subjects

D Nutt

Publications and source records attributed to D Nutt.

At least 55 records · Page 3Linked to original sources
PubMed1989

Benzodiazepines in the treatment of alcoholism.

This chapter comprises three sections that cover the main aspects of benzodiazepines and alcohol: (1) the basic pharmacology of benzodiazepines; (2) use of benzodiazepines in the treatment of withdrawal; and (3) the use of benzodiazepines in treating alcoholics. The basic studies suggest that a major site of action of alcohol may be the GABA/benzodiazepine receptor complex and that compensatory alterations in this complex may underly withdrawal. In the section on alcohol withdrawal, interactions between the GABA/benzodiazepine receptor complex, sympathetic nervous system, and hypothalamic-pituitary-adrenal axis are discussed. Use of benzodiazepines in the treatment of the alcohol withdrawal syndrome are reviewed, including the possibility that the benzodiazepines may prevent withdrawal-induced "kindling." Lastly, we review indications for, and efficacy of, benzodiazepines in long-term treatment of patients with alcoholism. Benzodiazepines are not indicated for the treatment of alcoholism. Furthermore, they have very few indications in alcoholics and their dependency-producing potency has to be appreciated when they are used in patients with alcoholism.

Alcohol Drinking↗
PubMed1988

Alpha-2-adrenoceptor function in alcohol withdrawal: a pilot study of the effects of iv. clonidine in alcoholics and normals.

Central alpha-2-adrenoceptor function was studied in seven withdrawing alcoholics and compared with seven normal controls using the clonidine challenge test. The alcoholic group had significantly elevated basal levels of blood pressure and plasma 3-methoxy-4-hydroxy-phenyl glycol. The percentage of fall in blood pressure produced by clonidine was blunted in the alcoholics. There was disruption of the neuroendocrine effects of clonidine on growth hormone release. Physiological indices of withdrawal, in particular plasma 3-methoxy-4-hydroxyphenyl glycol and blood pressure correlated with measures of previous withdrawal experiences, supporting the idea that kindling might occur with repeated episodes of withdrawal.

Adult↗
PubMed1988

Circadian rhythms of cortisol during alcohol withdrawal.

The authors have investigated the function of the hypothalamic-pituitary-adrenocortical (HPA) axis during and after withdrawal from alcohol. 24 hour rhythms of cortisol were abnormal in that elevated levels were seen throughout the day in patients with moderate to severe, but not mild, withdrawal. This abnormality of circadian secretion of cortisol, which is similar to that seen in Cushing's syndrome and post-operative trauma, returned to normal after a period of one week of abstinence on their in-patient ward. Such excessive secretion of cortisol may explain some of the complications of chronic alcoholism.

Adult↗
PubMed1987

The effects of chronic ritanserin treatment on sleep and the neuroendocrine response to L-tryptophan.

A previous study has shown that acute administration of the 5-HT2 receptor antagonist ritanserin doubles Slow Wave Sleep (SWS) and increases the prolactin (PRL) response to L-tryptophan (LTP). The present study investigated the effect of repeated ritanserin treatment on sleep, neuroendocrine response to LTP and 5-HT2 platelet receptor binding. After 2 weeks, ritanserin administration SWS was persistently increased but the PRL response to LTP was unchanged. Platelet 5-HT receptor binding was undetectable at the end of ritanserin treatment but recovered 2 weeks after drug withdrawal. The results suggest that ritanserin causes a sustained effect on the 5-HT mechanisms mediating SWS and on platelet 5-HT2 receptors. However, adaptation occurs to its effect on 5-HT-mediated neuroendocrine responses.

Adult↗
PubMed1987

The neuroendocrine effects of oral imipramine.

The release of growth hormone, prolactin and cortisol following oral imipramine was studied in nine fit young men. Imipramine 100 mg, but not 40 mg, led to reliable rises in the circulating levels of all three hormones in the majority of subjects. These responses are likely due to the enhancement of central noradrenergic and serotonergic function as a result of reuptake inhibition. The safety, sensitivity and reliability of these responses make imipramine 100 mg orally a potentially valuable neuroendocrine challenge test.

Administration, Oral↗
PubMed1987

Benzodiazepines, plasma MHPG and alpha-2-adrenoceptor function in man.

The effects of a single (15 mg) dose of diazepam, a 3-week course of diazepam (25 mg/d) and its withdrawal on plasma MHPG and the reduction produced by clonidine (1.5 micrograms kg-1 i.v.) were studied in 8 male volunteers. Chronic diagram reduced, but not significantly, plasma MHPG and attenuated the reduction produced Gyclonidine. During the withdrawal phase MHPG levels were significantly enhanced and the lowering produced by clonidine was also greater. These results support the hypothesis that some aspects of benzodiazepine withdrawal may reflect excessive central noradrenergic activity.

Brain↗
PubMed1987

NIH conference. Alcohol withdrawal and noradrenergic function.

Alcohol withdrawal syndrome is characterized by signs of overactivity of the sympathetic nervous system. Biochemical studies indicate that increased release of norepinephrine is associated with certain symptoms of alcohol withdrawal, and the severity of the withdrawal symptoms correlates positively with the amount of norepinephrine released. In the rat, the brain epinephrine concentration is reduced by alcohol, a phenomenon probably associated with both the intoxicating and rewarding effects of alcohol intake. Furthermore, intoxicating effects of alcohol can be reversed by inhibiting epinephrine synthesis in the rat brain. In this species, alcohol withdrawal is associated with profound depletion of epinephrine in the hypothalamus. When clonidine, a norepinephrine alpha-2-receptor agonist, was infused in alcoholics, these receptors were found to be subsensitive during alcohol withdrawal, and this subsensitivity may contribute to the syndrome. Repeated withdrawals may lead to "kindling" and thus further enhancement of noradrenergic overactivity. Pituitary responsiveness to corticotropin-releasing hormone, which is a central regulator of stress responses and increases the firing rate of brain noradrenergic neurons, is altered during alcohol withdrawal.

Alcoholism↗
PubMed1987

Clonidine in alcohol withdrawal: a pilot study of differential symptom responses following i.v. clonidine.

The effects of an i.v. bolus of clonidine (1.5 mg/kg) on withdrawal symptoms were studied in 7 male alcoholics, and compared with 7 normal controls. Clonidine reduced both subjective and objective measures of withdrawal but this only reached significance for scores of depression and muscle tension. In comparison with controls alcoholics in withdrawal showed reduced sedative effects of clonidine.

Adult↗
PubMed1986

Performance effects of diazepam during and after prolonged administration.

Seven volunteers received diazepam for a 3-week period, maximum dose rate 25 mg per day, and were tested on a variety of functions before, at two points during, and at two points after the period. Their performance was compared with that of 8 controls and was inferior on a number of measures. There was no indication either of habituation or of potentiation of the effects as the period continued. Equally, the low performance persisted for some time after administration ceased, although performance was on the whole better than during the experimental period. The particular measures showing deterioration suggested that the effects are similar to those of barbiturates as opposed to those of, for example, chlorpromazine.

Adult↗
PubMed1985

Septal driving of hippocampal theta rhythm: role of gamma-aminobutyrate-benzodiazepine receptor complex in mediating effects of anxiolytics.

In free-moving male rats, when the hippocampal theta rhythm is artificially driven by stimulation in the septum at frequencies between 5 and 10 Hz, the function relating frequency to the threshold current required to drive the theta rhythm has a minimum at 7.7 Hz. This minimum is eliminated by anxiolytic drugs. Dose-response curves for this effect are reported for chlordiazepoxide, diazepam and meprobamate. The effect of meprobamate was reversed by two gamma-aminobutyrateA antagonists, picrotoxin and bicuculline, which have previously been shown to be without effects of their own. The gamma-aminobutyrateB agonist, baclofen, also without effect on its own, blocked the elimination of the 7.7-Hz minimum caused by the gamma-aminobutyrateA agonist, muscimol. The beta-carboline, ethyl-beta-carboline-3-carboxylate, had mixed agonist/antagonist properties, blocking the effects of chlordiazepoxide, diazepam and muscimol (though not sodium amylobarbitone) but itself acting like a benzodiazepine. Coupled with earlier data, these findings support a role for gamma-aminobutyrate receptors in mediating the effects of anxiolytic drugs.

Animals↗