John Hyttel

Bio: John Hyttel is an academic researcher from Lundbeck. The author has contributed to research in topics: Dopamine & Agonist. The author has an hindex of 42, co-authored 103 publications receiving 7747 citations.

Citalopram--pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity.

Abstract: 1 Citalopram (Lu 10-171), a new bicyclic phthalane derivative, is an extremely potent inhibitor of neuronal serotonin (5-HT) uptake but has no effect on the uptake of noradrenaline (NA) and dopamine (DA) 2 Citalopram has no antagonistic activity towards DA, NA, 5-HT, histamine, gamma aminobutyric acid (GABA), acetylcholine, and morphine receptors In this way it clearly deviates from many old and new antidepressant drugs which have antagonistic effects towards some of these transmitters 3 In contrast to many tricyclic antidepressants citalopram is devoid of cardiotoxic effects, even when animals are exposed to concentrations far above the therapeutic level 4 In man citalopram is metabolized to compounds which are also potent 5-HT-uptake inhibitors without effect of NA uptake and which are found in lower concentrations than citalopram itself 5 In account of its extreme specificity as a 5-HT-uptake inhibitor citalopram should be considered as an experimental tool of the utmost importance In preliminary clinical experiments citalopram has shown a clear antidepressant effect This property together with the absence of troublesome anticholinergic adverse effects and cardiotoxic effects also make citalopram a most promising antidepressant drug

Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs).

Abstract: Established antidepressants including tricyclic antidepressants (TCAs), tetracyclic antidepressants and monoamine oxidase inhibitors (MAOIs) affect a series of neurotransmitter functions. In the debate of clinical efficacy much attention has focused on the uptake of noradrenaline (NA) and serotonin (5-HT) as a means to increase neuronal activity. Most antidepressants, whether classic or new, inhibit the uptake of either one or the other or both transmitters. Besides that, all of the classical antidepressants potently inhibit a series of neurotransmitter receptors. A series of newer antidepressants preferentially increase 5-HT transmission by inhibiting 5-HT uptake. Selective serotonin reuptake inhibitors (SSRIs) are those which preferably inhibit 5-HT uptake compared with NA, and which at the same time have no or only slight effect on other uptake mechanisms, neurotransmitter receptors, enzymes, etc. Five SSRIs are currently marked, i.e. citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. They all fulfil the above-mentioned criteria. Citalopram is the most selective 5-HT-uptake inhibitor, whereas paroxetine is the most potent. By and large the rank order of selectivity is equal in in vitro studies, in biochemical in vivo studies and in behavioural studies. Selectivity and potency for 5-HT uptake do not coincide. The selectivity of SSRIs is also founded on the lack of inhibition of receptors for different neurotransmitters, e.g. acetylcholine, histamine, NA, 5-HT or dopamine (DA), as well as monoamine oxidase (MAO). Citalopram, fluoxetine and sertraline are metabolized to compounds possessing similar properties as the parent drugs, whereas this is not the case with the metabolites of fluvoxamine and paroxetine. Upon repeated administration SSRIs maintain the selective and potent inhibition of 5-HT uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding.

Abstract: 1. The present survey compares the effects of antidepressants and their principal metabolites on reuptake of biogenic amines and on receptor binding. The following antidepressants were included in the study: the tricyclic antidepressants amitriptyline, dothiepin, and lofepramine and the atypical antidepressant bupropion, which all have considerable market shares in the UK and/or US markets; the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and the recently approved antidepressants venlafaxine and nefazodone.

Multiple receptors for dopamine.

Abstract: Pharmacological and biochemical criteria can be used to separate those dopamine receptors which are linked to the enzyme adenylyl cyclase and those which are not.

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...

Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).

Abstract: Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ Alexander E. Sorochinsky, Santos Fustero,*,‡,§ Vadim A. Soloshonok,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Av. Vicente Andreś Estelleś, 46100 Burjassot, Valencia, Spain Laboratorio de Molećulas Orgańicas, Centro de Investigacioń Príncipe Felipe, C/ Eduardo Primo Yuf́era 3, 46012 Valencia, Spain Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Alameda Urquijo, 36-5 Plaza Bizkaia, 48011 Bilbao, Spain Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv-94, Ukraine

Prolactin: Structure, Function, and Regulation of Secretion

Abstract: Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.