New anxiolitics in development

Mosconi, Margherita; Chiamulera, Cristiano; Zerbini, O.; Recchia, G

doi:10.1016/1043-6618(92)91094-w

Cited by 5 publications

(5 citation statements)

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“…Although the neuromolecular mechanisms underlying the anxiety reducing effects of alcohol are not entirely clear, interactions with both gamma-amino-butyric acid (GABA) receptors (Mosconi et al 1993;Prunell et al 1994b;Luddens and Korpi 1995;Moy et al 1997) and corticotropin releasing factor (CRF) (Baldwin et al 1991;Rassnick et al 1993;Menzaghi et al 1994) have been suggested. The possibility of an interaction of alcohol with NPY has not been previously entertained, and neither behavioral nor electrophysiological experiments have been accomplished which have evaluated the effects of ethanol and NPY in combination.…”

Section: Introductionmentioning

confidence: 98%

Are some of the effects of ethanol mediated through NPY?

1998

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Central administration of neuropeptide Y (NPY) in low concentrations has been shown to produce anxiolysis and suppression of locomotor activity, a behavioral profile not dissimilar to that of ethanol. The present study was conducted to ascertain whether NPY and ethanol have similar electrophysiological profiles and to evaluate the combined actions of NPY and ethanol. Eighty-five Wistar rats were stereotaxically implanted with electrodes aimed at dorsal hippocampus, amygdala, and frontal cortex. Rats were administered NPY [or saline (SAL)] intracerebroventricularly (i.c.v.) whereas the doses of alcohol (or SAL) were given intraperitoneally (i.p.). Two doses of alcohol (0.75, 1.5 g/kg) and two doses of NPY (1, 3 nmol) were given alone and in combination. Drug effects were assessed using event related potentials (ERP) recorded in response to an auditory "oddball" plus noise paradigm between 30 and 40 min post-drug. Multivariate analyses of variance (MANOVA) revealed that NPY produced a significant decrease in the amplitude and increase in the latency of the N1 component in cortex and a decrease in the amplitude of the P3 component in amygdala, but no overall effects in hippocampus. Ethanol produced identical effects to NPY on the N1 and P3 components of the ERP in cortex and amygdala. Combined administration of EtOH and NPY (1 nmol) produced effects equivalent to those seen following the higher doses of NPY (3 nmol) or EtOH (1.5 g/kg). These studies demonstrate that NPY and ethanol have a similar electrophysiological profile. In addition, the combined administration of NPY and ethanol produced additive effects.

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Section: Introductionmentioning

confidence: 98%

Are some of the effects of ethanol mediated through NPY?

1998

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“…There are several lines of evidence for a role of CCK in anxiety and panic attacks, and data also indicate that specific agonists to brain CCK(2) receptors produce anxiogenic-like effects while CCK(2) antagonists elicit anxiolytic-like responses [141][142][143][144].…”

Section: Neurotransmitter Systems and Neuronal Messengers Implicated mentioning

confidence: 99%

Neurobiology of Anxiety

Tóth

Zupan

2007

Handbook of Contemporary Neuropharmacology

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Anxiety/fear is a normal reaction to threatening situations and it represents a physiologically protective function. Anxiety/fear is often manifested as avoidance and is also characterized by overt sympathetic reactions. Pathological anxiety is a level of anxiety that is disproportionate to the threat and can be manifested even in the absence of threat. In clinical practice, categorical systems set the boundary at which a particular level of anxiety becomes an anxiety disorder. Although a genetic contribution to anxiety disorders has long been suspected, it is only recently that genetic polymorphisms in various neurotransmitter and neuromodulatory systems have been linked to anxiety disorders. Still, the contribution of these factors is relatively small to the overall disease phenotype and the complex interaction between genetic factors and the environment will ultimately explain the development of susceptibility to anxiety. Genetic and biochemical studies, combined with the analysis of mouse strains with induced genetic mutations implicate multiple neurobiological processes in anxiety disorders. Although the association of neurotransmitters and their receptors with anxiety‐like behavior is not surprising, cytokines and cell adhesion molecules were also identified as modulators of anxiety. Furthermore, intracellular signaling pathways and their target genes were linked to anxiety allowing the assembly of specific “anxiety” pathways. It is apparent that anxiety‐related pathways and processes involve communication between various neurons that, via signaling pathways, eventually converge onto regulation of transcription and/or translation. The proper function of these pathways is especially crucial during early postnatal development and one can hypothesize that abnormalities in these pathways at any level lead to, via altered gene expression, to changes in neuronal morphology and/or function. Importantly, all commonly used anxiolytic drugs can be integrated into this model implying that anxiolytic drugs target and modulate the molecular and cellular pathways which establish and/or control the level of anxiety.

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“…As of 1996, a number of related compounds acting through 5-HT 1A receptor partial agonism and antagonism were in various stages of clinical development for this indication. Furthermore, exploratory approaches focusing on cholecystokinin receptor antagonism, 5-HT 2 receptor antagonism, 5-HT 3 receptor antagonism, neuropeptide Y 1 receptor agonism, neuronal nicotinic acetylcholine receptor subtype agonism, melatonin receptor agonism, N-methyl-D-aspartate receptor antagonism, as well as neurosteroids (eg, epalons) as the basis of novel treatment strategies for anxiety disorders and/or insomnia were actively being followed preclinically and even in clinical investigations (114). Finally, increasing attention is being given to the positive results from clinical investigations of various marketed antidepressants, eg, tricyclics and monoamine-oxidase inhibitors, in panic disorder and phobias (115).…”

Section: Other Sedative Agentsmentioning

confidence: 99%

Psychopharmacological Agents

Martin

Godel

Hunkeler

et al. 2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Martin, James R.; Godel, T.; Hunkeler, W.; Jenck, F.; Moreau, J‐L.; Sleight, A. J.; and Widmer, U. (F. Hoffmann‐La Roche Ltd.). A number of important advances have occurred in the understanding and the treatment of disorders of the central nervous system including mood disorders, schizophrenia, anxiety disorders, insomnia, substance use disorders, and dementias. The plethora of novel drugs act by means of diverse neurobiological mechanisms and represent a great diversity of chemical structures. Along with improvements in the therapeutic index of anxiolytics, sedative–hypnotics, antidepressants, and antipsychotics, some progress has also been made in the search for drugs effective in the treatment of substance use disorders, as well as Alzheimer's disease and other dementias. Nonetheless, such improvements in symptomatic therapy have not been accompanied by the discovery of effective etiological and pathophysiological interventions. It is from here that the successful psychopharmacological agents of the future must come.

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New anxiolitics in development

Cited by 5 publications

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Are some of the effects of ethanol mediated through NPY?

Are some of the effects of ethanol mediated through NPY?

Neurobiology of Anxiety

Psychopharmacological Agents

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