Mark John Millan

..In conclusion, [3H]GR125,743 is an appropriate tool for the radiolabelling of native, rat 5-HT(1B) receptors and permitted determination of the affinities of an extensive series of ligands at these sites...

..Furthermore, in line with its in vitro actions, it more potently blocks cerebral populations of D(3) versus D(2) receptors...

..The novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors and as an antagonist at serotonin (5-HT)(2C) receptors...

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..Although the relationship between these actions awaits further clarification, these data underpin the relevance of D1 receptors to CNS disorders in which cholinergic transmission and social cognition are disrupted...

..This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'...

..This article critically discusses these issues, highlighting the challenges and opportunities for improving cognition in individuals suffering from psychiatric disorders...

..In conclusion, S32212 displays a functional profile consistent with improved mood and cognitive performance, together with satisfactory tolerance...

..Its promising profile in preclinical models potentially relevant to the treatment of depression is described in J Pharmacol Exp Ther 340:765-780, 2012...

..Finally, a diversity of multi-target strategies is proposed for the more efficacious and rapid control of core and co-morbid symptoms of depression, together with improved tolerance relative to currently available agents...

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..Activation of "co-agonist" N-methyl-D-aspartate (NMDA) and Glycine(B) sites is mandatory for the operation of NMDA receptors, which play an important role in the control of mood, cognition and motor function...

..The neurokinin-1 antagonist, GR205,171, mimics the interoceptive properties of reboxetine, possibly reflecting its elevation of extracellular levels of NE in corticolimbic structures...

..Its actions involve both blockade of postsynaptic 5-HT(1A) receptors and engagement of 5-HT(1A) autoreceptors...

..The role of dopamine D(3)/D(2) receptors in the control of locomotion is poorly understood...

..Its actions are more pronounced than those of ropinirole and principally involve engagement of D(2) receptors...

..Although activation of D(2) receptors is crucial to the motor actions of S32504, engagement of D(3) receptors contributes to its neuroprotective properties...

..J Pharmacol Exp Ther 309:936-950, 2004a; Millan et al., J Pharmacol Exp Ther 309:903-920, 2004b; Millan et al., J Pharmacol Exp Ther 309:921-935, 2004c)...

..These data support the pertinence of D(3) receptors as a target for treatment of disorders in which cognitive function is compromised...

..The present article discusses the functionally and clinically important interplay amongst miRNAs and serotoninergic mechanisms in the brain, peripheral organs and cancerous tissue...

..It will be of interest to determine whether the neutral antagonist properties of agomelatine are related to its favourable clinical profile of antidepressant properties with few side-effects and no discontinuation syndrome...

..These data underpin interest in D(3) receptor blockade as a strategy for improving cognitive performance in CNS disorders like schizophrenia and Parkinson's disease...

..The article concludes by highlighting perspectives for clarifying the mechanisms of action of piribedil and other antiparkinson agents, and for optimizing their clinical exploitation...

..This review discusses the discovery and development of dual- and triple-acting antidepressants, focusing on novel concepts and new drugs disclosed over the last 2 to 3 years...

..It also reviews developmental and genetic risk factors for schizophrenia and their experimental modeling in rodents, with a particular emphasis on sensorimotor gating and cognitive deficits...

..In view of the diversity of transduction mechanisms engaged by 5-HT, much of this discussion is relevant to other classes of G-protein-coupled receptors...

..This profile differentiates MCH1 receptor antagonists from conventional anxiolytic and antidepressant agents...

..In comparison with clinically available agents, S33138 displays, thus, a distinctive and promising profile of potential antipsychotic properties...

..In conclusion, S33138 possesses a distinctive receptor-binding profile and behaves, in contrast to clinically available antipsychotics, as a preferential antagonist at hD(3) versus hD(2) receptors...

..Although the D(3)/D(2) agonist and antiparkinsonian agent ropinirole mimicked the profile of S32504, it was less potent. In conclusion, S32504 is a potent and selective agonist at dopamine D(3) and D(2) receptors...

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..6). In conclusion, piribedil displays essentially antagonist properties at cloned, human and cerebral, rat alpha(2)-ARs. Blockade of alpha(2)-ARs may, thus, contribute to its clinical antiparkinsonian profile...

..It enhances extracellular levels of 5-HT and NE throughout corticolimbic structures and selectively elevates dialysis levels of DA in frontal cortex versus subcortical regions...

..It exerts its actions more potently than venlafaxine and clomipramine, and its overall profile is distinct from those of citalopram and reboxetine...

..Adrenergic mechanisms may, thus, be involved in the potential antidepressant and other functional properties of NK(1) receptor antagonists...

..In conclusion, an innovative multivariate analysis revealed marked heterogeneity in binding profiles of antiparkinson agents. Actions at sites other than hD(2) receptors likely participate in their (contrasting) functional profiles...

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..In conclusion, CP154,526 and DMP695 possess a common and distinctive profile of anxiolytic action expressed in the absence of an intrinsic influence upon monoamine release...

..Indeed, in view of its clinical relevance, broader exploitation of the Vogel conflict test in the identification of novel classes of anxiolytic agents, and in the determination of their mechanisms of action, would prove instructive...

..Knowledge of descending pathways has increased exponentially in recent years, so this is an opportune moment to survey their operation and therapeutic relevance to the improved management of pain...

..In conclusion, S41744 is an innovative NK(1) antagonist/5-HT reuptake inhibitor justifying further evaluation for treatment of stress-related disorders...

..Recently, we demonstrated that SSRIs, such as citalopram, enhance LA in mice exposed to a novel environment...

..In conclusion, in contrast to melatonin, agomelatine behaves as an antagonist at 5-HT2B and 5-HT2C receptors: blockade of the latter reinforces frontocortical adrenergic and dopaminergic transmission...

..This article reviews the complex role of GLY(B) sites/NMDA receptors and their endogenous ligands in the pathogenesis and treatment of psychotic states...

..Although the biological bases of this behaviour remain unclear, these observations underpin the contention that NK(1) receptors may be implicated in affective disorders...

..Combined NK(1) receptor antagonism/5-HT reuptake inhibition may offer advantages in the management of depressed and anxious states...

..Activation of mesocortical dopaminergic pathways may be involved in the influence of NK(1) antagonists upon mood...

..In conclusion, vestipitant is a potent NK(1) receptor antagonist: its actions support the utility of NK(1) receptor blockade in the alleviation of anxiety and, possibly, depression...

..5-HT6 receptor antagonists improve cognitive processes in rodents. However, their site(s) of action remains unexplored and their influence upon social memory has been little investigated...

..Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their functional profiles in vivo...

..Further, they support the interest of DRL 72-s procedures for the characterisation of diverse classes of antidepressant agent...

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..In contrast, partial agonists favor h5-HT(1A) receptor signaling to Galpha(i3) over a wide concentration range, whereas inverse agonists inhibit constitutive Galpha(i3) activation...

..g. S16924 and ziprasidone), via intermediate (e.g. clozapine) to low (e.g. haloperidol). Differential modulation of 5-HT(1A) receptor-coupled MAPK may contribute to their contrasting functional profiles...

..Although an influence upon arousal and/or anxiety is likely related to the increase in LA, the functional significance of this response requires additional elucidation...

..Employing this novel technique, the typical and atypical antipsychotics, clozapine and haloperidol, respectively, both exhibited antagonist properties at dopamine D1 receptors...

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..In conclusion, selective blockade of 5-HT(2A) receptors by MDL100,907 elicits a discriminative stimulus in rats which appears to be specifically mediated via 5-HT(2A) as compared with 5-HT(2B) and 5-HT(2C) receptors...

..These data demonstrate antagonist properties of DMP695 at central CRF(1) receptors excitatory to ascending noradrenergic neurones, an action which may contribute to its distinctive profile of anxiolytic properties...

..In conclusion, antiparkinson agents display diverse agonist and antagonist properties at multiple subtypes of D(2)-like receptor and alpha(1)/alpha(2)-AR, actions, which likely contribute to their contrasting functional profiles...

..In conclusion, h5-HT(2C) receptors couple to both Gq/11 and Gi(3) in CHO cells, and efficacy for G protein subtype activation is both ligand- and receptor reserve-dependent...

..In conclusion, S18616 elicits a robust DS in rats that principally reflects engagement of alpha2A-ARs. This novel procedure should prove useful in the characterisation of psychoactive drugs which interact with alpha2-ARs...

..In conclusion, principally via recruitment of D2 receptors, piribedil exerts robust and specific antidepressant-like actions in diverse rodent models...

..Moreover, they emphasize the continuing need for alpha(2)-AR subtype-selective antagonists in order to define further the roles and therapeutic relevance of halpha(2A)-, halpha(2B)-, and halpha(2C)-AR...

..A role of dopaminergic terminals in the reuptake of NA likely explains the elevation in its levels elicited by DA reuptake-inhibitors and D3/D2 receptor antagonists...

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..PAMs more markedly enhanced efficacy of coupling to Go versus Gi(1/3). It will be of interest to confirm these observations employing complementary techniques and to evaluate their potential therapeutic significance...

..Conversely, when the primary amide function was integrated in a lactam ring, an enhancement of affinity and selectivity was attained for the five-membered ring lactam but also for its five-membered ring lactone analogue...

..Although several antagonists clearly differentiated h5-HT2C from h5-HT2B receptors under these conditions, highly selective agonists remain to be identified...

..Though 5-HT6 receptor blockade is not indispensable for therapeutic efficacy, it may well play a role in the functional actions of certain antipsychotic agents...

..63), into the FCX though it was also active (0.63) in the nucleus accumbens. These data suggest that D(3) receptors modulating social recognition are localized in FCX, and underpin their pertinence as targets for antipsychotic agents...

..Serotonin (5-HT)(2C) receptors are implicated in the control of mood, and their blockade is of potential interest for the management of anxiodepressive states...

..Though interoceptive properties of antidepressants have been described, discriminative stimulus (DS) properties of mirtazapine, which does not affect monoamine reuptake, remain uncharacterized...

..However, significant differences were seen regarding the involvement of PLC, calmodulin, and ERK1/2...

..The first clinical studies for the evaluation of this hypothesis have recently got underway...