David B Menkes

Bio: David B Menkes is an academic researcher from University of Auckland. The author has contributed to research in topics: Medicine & Serotonin. The author has an hindex of 31, co-authored 146 publications receiving 4071 citations. Previous affiliations of David B Menkes include University of Otago & University of Melbourne.

Receptor Sensitivity and the Mechanism of Action of Antidepressant Treatment: Implications for the Etiology and Therapy of Depression

Abstract: • Considerable evidence suggests that the acute effects of antidepressant treatments on brain norepinephrine (NE) and serotonin (5-HT) systems cannot account fully for their delayed therapeutic action. This review evaluates the effects of long-term antidepressant treatment on biogenic amine metabolism and on various indexes of presynaptic and postsynaptic receptor function. In contrast to variable effects on NE and 5-HT turnover and on presynaptic receptor sensitivity, almost all long-term antidepressant treatments produce consistent alterations in a number of measures of postsynaptic amine receptor sensitivity. Longterm treatment has been found to reduce β-adrenergic sensitivity while enhancing responses to serotonergic and α-adrenergic stimulation, suggesting that modulation of receptor sensitivity may be a mechanism of action common to tricyclic antidepressants, "atypical" antidepressants, monoamine oxidase inhibitors, and electroconvulsive therapy. These findings provide support for hypotheses of amine receptor abnormalities in depression and indicate the need for expanded studies of amine receptor function in patients.

Efficacy and safety of antidepressants for children and adolescents

Abstract: How safe and effective are antidepressants in children and adolescents? The authors of this review have found disturbing shortcomings in the methods and reporting of trials of newer antidepressants in this patient group Antidepressants introduced since 1990, especially selective serotonin reuptake inhibitors and venlafaxine, have been used increasingly as first line treatment for depression in children.1 2 The safety of prescribingantidepressants to children (including adolescents) has been the subject of increasing concern in the community and the medical profession, leading to recommendations against their use from government and industry (box 1). In this paper, we review the published literature on the efficacy and safety of newer antidepressants in children. Having criticised the way in which Keller et al interpreted the results of their study,3 4 we sought to check the quality of methods and reporting of other published trials of newer antidepressants in children (box 2). Of seven published randomised controlled trials of newer antidepressants for depressed children published in refereed journals, six used a placebo control.35–9 We analysed eachstudy's methods and the extent to which authors' conclusions were supported by data. The seventh study, which compared a newer antidepressant with a tricyclic antidepressant without finding significant difference,10 was not included in the analysis but appears in the table on bmj.com. ### Box 1: Warnings about antidepressants in children June 2003—Letter from GlaxoSmithKline to all medical practitioners in the United Kingdom actively discouraging the use of paroxetine in patients less than 18 years of age, on the basis of recently disclosed trial results showing unacceptable risk of serious adverse effects,including hostility and suicidality.www.researchprotection.org/risks/PaxilRisks0603.html(accessed 17 Mar 2004) June 2003—Warning from the UK Committee on Safety of Medicines against the use of paroxetine inchildren.www.mhra.gov.uk/news/2003/seroxat10603.pdf(accessed 1 Mar 2004) August 2003—Warnings about venlafaxine, promulgated by the manufacturer.www.effexor.com/pdf/Wyeth_HCP.pdf(accessed 30 Dec …

Guanosine triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment.

Abstract: Activation of adenylate cyclase by a stable guanosine 5'-triphosphate analog was augmented in brain membrane preparations from rats treated on a long-term basis with tricyclic antidepressants or electroconvulsive shock. These treatments may facilitate cyclase activation by promoting the interaction of the regulatory and catalytic subunits of the enzyme. This finding suggests a possible mechanism for the changes in sensitivity to various neurotransmitters seen after antidepressant administration.

Vitamin D deficiency.

Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Dopamine Receptors: From Structure to Function

Abstract: Missale, Cristina, S. Russel Nash, Susan W. Robinson, Mohamed Jaber, and Marc G. Caron. Dopamine Receptors: From Structure to Function. Physiol. Rev. 78: 189–225, 1998. — The diverse physiological actions of dopamine are mediated by at least five distinct G protein-coupled receptor subtypes. Two D1-like receptor subtypes (D1 and D5) couple to the G protein Gs and activate adenylyl cyclase. The other receptor subtypes belong to the D2-like subfamily (D2 , D3 , and D4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D1 and D5 receptors are intronless, but pseudogenes of the D5 exist. The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine s...