Serotonin Receptor Subtypes: Implications for Psychopharmacology

1991 ◽  
Vol 159 (S12) ◽  
pp. 7-14 ◽  
Author(s):  
P. J. Cowen
Keyword(s):  
Cognitive Processes ◽  
Serotonin Receptor ◽  
Antidepressant Treatment ◽  
Receptor Subtypes ◽  
Therapeutic Effects ◽  
Controlled Clinical Trials ◽  
Wide Range ◽  
Selective Ligands ◽  
Coupling Mechanisms ◽  
Therapeutic Possibilities

Serotonin (5-HT) interacts with multiple brain 5-HT receptor subtypes to influence a wide range of behaviours. Three main families of 5-HT receptors (5-HT1, 5-HT2 and 5-HT3) have been described which differ in their binding affinity for selective ligands, their receptor-effector coupling mechanisms, and the behavioural processes they regulate. Nevertheless, manipulation of several different 5-HT receptor subtypes (5-HT1A, 5-HT1c, 5-HT2 and 5-HT3) may produce anxiolytic effects; 5-HT1A and 5-HT2 receptors may be involved in the aetiology of major depression and the therapeutic effects of antidepressant treatment; and 5-HT3 receptors have been linked to reward mechanisms and cognitive processes. These advances offer therapeutic possibilities, the value of which can only be satisfactorily assessed by controlled clinical trials.

scholarly journals Different Serotonin Receptor Agonists Have Distinct Effects on Sound-Evoked Responses in Inferior Colliculus

2006 ◽  
Vol 96 (5) ◽  
pp. 2177-2188 ◽  
Author(s):  
Laura M. Hurley
Keyword(s):  
Inferior Colliculus ◽  
Auditory Processing ◽  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Frequency Tuning ◽  
Receptor Subtypes ◽  
Tuning Curves ◽  
Wide Range ◽  
Selective Agonists ◽  
Auditory Nucleus

The neuromodulator serotonin has a complex set of effects on the auditory responses of neurons within the inferior colliculus (IC), a midbrain auditory nucleus that integrates a wide range of inputs from auditory and nonauditory sources. To determine whether activation of different types of serotonin receptors is a source of the variability in serotonergic effects, four selective agonists of serotonin receptors in the serotonin (5-HT) 1 and 5-HT2 families were iontophoretically applied to IC neurons, which were monitored for changes in their responses to auditory stimuli. Different agonists had different effects on neural responses. The 5-HT1A agonist had mixed facilitatory and depressive effects, whereas 5-HT1B and 5-HT2C agonists were both largely facilitatory. Different agonists changed threshold and frequency tuning in ways that reflected their effects on spike count. When pairs of agonists were applied sequentially to the same neurons, selective agonists sometimes affected neurons in ways that were similar to serotonin, but not to other selective agonists tested. Different agonists also differentially affected groups of neurons classified by the shapes of their frequency-tuning curves, with serotonin and the 5-HT1 receptors affecting proportionally more non-V-type neurons relative to the other agonists tested. In all, evidence suggests that the diversity of serotonin receptor subtypes in the IC is likely to account for at least some of the variability of the effects of serotonin and that receptor subtypes fulfill specialized roles in auditory processing.

Synthesis and Antibacterial / Anticancer Activities of Compounds Containing Pyrazole Ring Linked to Piperazines

2020 ◽  
Vol 16 (4) ◽  
pp. 419-431
Author(s):  
Kishore K. Valluri ◽  
Tejeswara R. Allaka ◽  
IV Kasi Viswanath ◽  
Nagaraju PVVS
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Pyrazole Ring ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Parent Molecule ◽  
Wide Range

Background: Many pyrazole piperazine derivatives are known to exhibit a wide range, thus being attractive for the drug design and synthesis of interesting class of widely studied heterocyclic compounds. It is therefore necessary to devote continuing effort for the identification and development of New Chemical Entities (NCEs) as potential antibacterial and anticancer agents to address serious health problems. Methods: A series of new compounds containing pyrazole ring linked to a piperazine hydrochloride moiety were synthesized and screened for their antibacterial activity, cytotoxicity of novel scaffolds are described by variation in therapeutic effects of parent molecule. The structure variants were characterized by using a blend of spectroscopic 1H NMR, 13C NMR, IR, Mass and chromatographic techniques. Results: When tested for in vitro antibacterial and anticancer activities, several of these compounds showed good activities. The target compounds 9b, 9a and 9e exhibited a high degree of anticancer activity against human colon cancer cell line Caco-2 and human breast cancer cell line MDAMB231. Further, 9a, 9b, 9d, and 9h showed better activity towards four medically relevant organisms; Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Klebsiella Species compared to CPF. In the present investigation, cheminfomatics tools Molinspiration, 2003 and MolSoft, 2007 for the prediction of insilico molecular properties and drug likeness for the target compounds 9a-h was evaluated and positive results were observed. Conclusion: Our study revealed that the molecular framework presented here could be a useful template for the identification of novel small molecules as promising antibacterial/ anticancer agents.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

scholarly journals Potential Role of Caffeine in the Treatment of Parkinson’s Disease

2016 ◽  
Vol 10 (1) ◽  
pp. 42-58 ◽  
Author(s):  
Mohsin H.K. Roshan ◽  
Amos Tambo ◽  
Nikolai P. Pace
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Clinical Trials ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Muscle Rigidity ◽  
Therapeutic Effects ◽  
Motor Symptoms ◽  
Wide Range

Parkinson’s disease [PD] is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from bothin vivoandin vitrostudies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2Areceptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials.

scholarly journals Metacognition: A new cognitive paradigm

Psihologija ◽  
2004 ◽  
Vol 37 (2) ◽  
pp. 149-161 ◽  
Author(s):  
Milos Kankaras
Keyword(s):  
Cognitive Functioning ◽  
Cognitive Processes ◽  
Cognitive Activity ◽  
Human Mind ◽  
Short Period ◽  
Wide Range ◽  
Thinking Processes ◽  
And Behavior ◽  
And Control ◽  
Metacognitive Experiences

This article reviews concept of metacognition, defined as: (a) knowledge about ones own cognitive activity, (b) strategies to monitor and regulate cognitive activity and behavior, and (c) subjective or metacognitive experiences which comes from some changes or temporary difficulties in cognitive functioning. While describing different conceptualizations of metacognition, its development, fields of application, relation with intelligence, and its constrictions and ambiguity, we attempt to present new and emerging metacognitive paradigm, which is, for a relatively short period, succeeded to improve, expand, and redefine wide range of theoretical and practical fields in psychology, on new and original way. How do we become conscious of our own cognitive processes? What role and significance that consciousness has, what is the functional level above thinking processes and how that level, which monitor and control cognitive activity, works. Metacognition is concept that presents, as so far, the most important insight in those human mind areas, which, although very important, remained on the margin of psychological investigations until now.

scholarly journals The responsiveness of gait and balance outcomes to disease progression in Friedreich ataxia

2021 ◽  
Author(s):  
Sarah C Milne ◽  
Seok Hun Kim ◽  
Anna Murphy ◽  
Jane Larkindale ◽  
Jennifer Farmer ◽  
...  
Keyword(s):  
Effect Size ◽  
Rating Scale ◽  
Friedreich Ataxia ◽  
Correlation Coefficients ◽  
Berg Balance Scale ◽  
Therapeutic Effects ◽  
Balance System ◽  
Gait Parameters ◽  
Wide Range ◽  
Daily Step Count

Objective: To identify gait and balance measures that are responsive to change during the timeline of a clinical trial in Friedreich ataxia (FRDA) we administered a battery of potential measures three times over a 12-month period. Methods: Sixty-one ambulant individuals with FRDA underwent assessment of gait and balance at baseline, six months and 12 months. Outcomes included: GAITRite spatiotemporal gait parameters; Biodex Balance System Postural Stability Test (PST) and Limits of Stability; Berg Balance Scale (BBS); Timed 25 Foot Walk Test; Dynamic Gait Index (DGI); SenseWear MF Armband step and energy activity; and the Friedreich Ataxia Rating Scale Upright Stability Subscale (FARS USS). The standardised response mean (SRM) or correlation coefficients were reported as effect size indices for comparison of internal responsiveness. Internal responsiveness was also analysed in subgroups. Results: SenseWear Armband daily step count had the largest effect size of all the variables over six months (SRM=-0.615), while the PST medial-lateral index had the largest effect size (SRM=0.829) over 12 months. The FARS USS (SRM=0.824) and BBS (SRM=-0.720) were the only outcomes able to detect change over 12 months in all subgroups. The DGI was the most responsive outcome in children, detecting a mean change of -2.59 (95% CI -3.52 to -1.66, p<0.001, SRM=-1.429). Conclusions: The FARS USS and BBS are highly responsive and can detect change in a wide range of ambulant individuals with FRDA. However, therapeutic effects in children may be best measured by the DGI.

scholarly journals Distinct evolutionary trajectories of V1R clades across mouse species

2020 ◽  
Author(s):  
Caitlin H Miller ◽  
Polly Campbell ◽  
Michael J Sheehan
Keyword(s):  
Positive Selection ◽  
House Mouse ◽  
Gene Family Evolution ◽  
Specific Gene ◽  
Receptor Subtypes ◽  
Gene Repertoire ◽  
Social Signals ◽  
Functional Roles ◽  
Wide Range ◽  
Evolutionary Trajectories

Abstract BACKGROUND: Many animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus . We report the extent of gene repertoire turnover and conservation among species and clades, as well as the prevalence of positive selection on gene sequences across the V1R tree. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution. RESULTS: We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. We identify putative species-specific gene expansions, including a large clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future study. We find evidence for distinct evolutionary processes across different clades, from largescale turnover to highly conserved repertoires. Patterns of positive selection are similarly variable, as some clades exhibit abundant positive selection while others display high gene sequence conservation. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results reveal clades with receptors detecting female reproductive status are among the most conserved across species, suggesting an important role in V1R chemosensation. CONCLUSION: Analysis of clade-level evolution is critical for understanding species’ chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of receptors.

Effects of Response Range in Frequency Judgments of Common versus Uncommon Events

1996 ◽  
Vol 82 (3_suppl) ◽  
pp. 1371-1376 ◽  
Author(s):  
Kimihiko Yamagishi
Keyword(s):  
Cognitive Processes ◽  
High Frequency ◽  
Narrow Range ◽  
Frequency Estimation ◽  
Low Frequency ◽  
Social Facts ◽  
Frequency Judgments ◽  
Response Range ◽  
Wide Range ◽  
Wide Condition

Frequency estimation of social facts was compared between two methods of response elicitation. In the “narrow range” method, respondents answered questions like: “Out of 100 instances, how many instances belong to category X?”. In the “wide range” method, the same question was asked regarding “Out of 10,000.” A previous study in 1994 showed that judged frequencies were proportionally greater in the narrow condition than in the wide condition when subjects estimated the occurrence of low-frequency events. These results were interpreted to reflect cognitive processes of anchoring, wherein judged frequencies he close to small numbers within particular response ranges. The current work extends this argument to high-frequency events. In such cases, judgments about high-frequency events would be reached by similar cognitive processes operating toward the opposite direction. Hence, I predicted that judged frequencies for high-frequency events would be proportionally greater in the wide than in the narrow condition. Results were mostly consistent with these predictions. The relation to previous research is discussed.

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