Central 5-HT2 antagonists: A preclinical evaluation of a therapeutic potential

1990 ◽  
Vol 2 (4) ◽  
pp. 101-109 ◽  
Author(s):  
T.F. Meert ◽  
F. Awouters
Keyword(s):  
Animal Models ◽  
Negative Symptoms ◽  
Tricyclic Antidepressants ◽  
Therapeutic Potential ◽  
Test Procedure ◽  
Therapeutic Effects ◽  
Preclinical Evaluation ◽  
Animal Models Of Depression ◽  
Animal Models Of Anxiety ◽  
Positive And Negative Symptoms

SummaryA preclinical evaluation is presented of the serotonin 5-HT2 antagonists ritanserin and risperidone. Whereas ritanserin is a relative selective 5-HT2 antagonist, risperidone is a potent 5-HT2 and catecholamine antagonist. The pharmacological differences between both drugs are also observed in the drug discrimination test procedure. Using DOM, d-amphetamine and cocaine. Ritanserin was found active in animal models of anxiety using natural aversive stimuli; and in animal models of depression. Clear differences were observed between ritanserin and the benzodiazepines and between ritanserin and the tricyclic antidepressants. Risperidone was active in animal models of psychosis. Risperidone has, as opposed to classical neuroleptics such as haloperidol, less risks of inducing a dopamine D2 overblockade. Clinically, ritanserin is described as a thymostenic agent.Risperidone is an antipsychotic with therapeutic effects on both the positive and negative symptoms of schizophrenia and with a reduced risk of extrapyramidal side-effects.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

scholarly journals Cannabinoids for the Treatment of Schizophrenia? A Balanced Neurochemical Framework for Both Adverse and Therapeutic Effects of Cannabis Use

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Carissa M. Coulston ◽  
Michael Perdices ◽  
Antony F. Henderson ◽  
Gin S. Malhi
Keyword(s):  
Negative Symptoms ◽  
Normal Population ◽  
Brain Regions ◽  
Cannabis Use ◽  
Future Research ◽  
Therapeutic Effects ◽  
Neuropsychological Performance ◽  
Neurobiological Substrates ◽  
History Of ◽  
Positive And Negative Symptoms

Recent studies have found that cannabinoids may improve neuropsychological performance, ameliorate negative symptoms, and have antipsychotic properties for a subgroup of the schizophrenia population. These findings are in contrast to the longstanding history of adverse consequences of cannabis use, predominantly on the positive symptoms, and a balanced neurochemical basis for these opposing views is lacking. This paper details a review of the neurobiological substrates of schizophrenia and the neurochemical effects of cannabis use in the normal population, in both cortical (in particular prefrontal) and subcortical brain regions. The aim of this paper is to provide a holistic neurochemical framework in which to understand how cannabinoids may impair, or indeed, serve to ameliorate the positive and negative symptoms as well as cognitive impairment. Directions in which future research can proceed to resolve the discrepancies are briefly discussed.

scholarly journals Saikosaponin D Ameliorates Mechanical Hypersensitivity in Animal Models of Neuropathic Pain

2020 ◽  
Vol 07 (04) ◽  
pp. e145-e149
Author(s):  
Gyeongbeen Lee ◽  
Yeon-Ju Nam ◽  
Woo Jung Kim ◽  
Bo Hye Shin ◽  
Jong Suk Lee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Oral Administration ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Receptor Potential ◽  
Repeated Administration ◽  
Therapeutic Effects ◽  
Mechanical Hypersensitivity ◽  
Pain Outcomes

AbstractWe have previously identified saikosaponins as transient receptor potential ankyrin 1 antagonists and showed that saikosaponin D improves neuropathic pain induced by the anticancer drug vincristine in mice. In order to gain more insight into the therapeutic effects of saikosaponin D, we tested saikosaponin D in animal models of neuropathic pain induced by either streptozotocin, which mimics diabetes, or paclitaxel, a commonly used chemotherapy treatment. Our findings indicate that although saikosaponin D improved pain outcomes in neuropathic pain models, the mechanisms underlying the therapeutic effects of saikosaponin D appear to differ between streptozotocin- and paclitaxel-induced pain. Streptozotocin-induced neuropathic pain was significantly alleviated 30 minutes after oral administration of saikosaponin D, while 1-day oral administration of saikosaponin D had little effect on paclitaxel-induced mechanical hypersensitivity. Attenuation of paclitaxel-induced mechanical hypersensitivity was evident only after repeated administration of saikosaponin D. Although the mechanisms underlying the therapeutic effects of saikosaponin D remain to be elucidated, our results shed new light on the therapeutic potential of saikosaponin D in the management of neuropathic pain caused by diabetes or chemotherapy.

scholarly journals Potential therapeutic effects of Nrf2 activators on intracranial hemorrhage

2021 ◽  
pp. 0271678X2098456
Author(s):  
Takahiko Imai ◽  
Hirofumi Matsubara ◽  
Hideaki Hara
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Intracranial Hemorrhage ◽  
Therapeutic Potential ◽  
Heme Oxygenase 1 ◽  
Therapeutic Effects ◽  
Secondary Brain Injury ◽  
Pathological Conditions ◽  
Poor Outcomes ◽  
Effective Drugs

Intracranial hemorrhage (ICH) is a devastating disease which induces high mortality and poor outcomes including severe neurological dysfunctions. ICH pathology is divided into two types: primary brain injury (PBI) and secondary brain injury (SBI). Although there are numerous preclinical studies documenting neuroprotective agents in experimental ICH models, no effective drugs have been developed for clinical use due to complicated ICH pathology. Oxidative and inflammatory stresses play central roles in the onset and progression of brain injury after ICH, especially SBI. Nrf2 is a crucial transcription factor in the anti-oxidative stress defense system. Under normal conditions, Nrf2 is tightly regulated by the Keap1. Under ICH pathological conditions, such as overproduction of reactive oxygen species (ROS), Nrf2 is translocated into the nucleus where it up-regulates the expression of several anti-oxidative phase II enzymes such as heme oxygenase-1 (HO-1). Recently, many reports have suggested the therapeutic potential of Nrf2 activators (including natural or synthesized compounds) for treating neurodegenerative diseases. Moreover, several Nrf2 activators attenuate ischemic stroke-induced brain injury in several animal models. This review summarizes the efficacy of several Nrf2 activators in ICH animal models. In the future, Nrf2 activators might be approved for the treatment of ICH patients.

The Effects of TMS on Animal Models of Depression, β-Adrenergic Receptors, and Brain Monoamines

CNS Spectrums ◽  
1997 ◽  
Vol 2 (1) ◽  
pp. 26-30 ◽  
Author(s):  
R.H. Belmaker ◽  
Nimrod Grisaru ◽  
Dorit Ben-Shahar ◽  
Ehud Klein
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Animal Models ◽  
Electroconvulsive Therapy ◽  
Clinical Studies ◽  
Adrenergic Receptors ◽  
Magnetic Stimulation ◽  
Therapeutic Effects ◽  
Brain Monoamines ◽  
Animal Models Of Depression ◽  
Β Adrenergic Receptors

AbstractIn initial studies using animal models of depression, we primarily focused on the similarities of transcranial magnetic stimulation (TMS) to electroconvulsive therapy (ECT). However, our investigations show that TMS has its own, unique, potentially diagnostic and therapeutic effects, distinct from those of ECT. These effects need further exploration in animal and clinical studies.

scholarly journals Therapeutic Potential of Pluripotent Stem Cell-derived Dopaminergic Progenitors in Parkinson's Disease: A Systematic Review Protocol

2020 ◽  
Author(s):  
Aliasghar Karimi ◽  
Mitra Elmi ◽  
Zahra Shiri ◽  
Hossein Baharvand
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Promising Alternative

Abstract Background: Parkinson's disease (PD) is the second most common age-dependent neurodegenerative disease that causes motor and cognitive disabilities. This disease is associated with a loss of dopamine content within the putamen, which stems from the degeneration of dopaminergic (DA) neurons in the Substantia Nigra pars Compacta (SNc). Several approved drugs are available that can effectively treat symptoms of PD. However, long-term medical management is often complicated and does not delay or halt disease progression. Alternatively, cell replacement strategies can address these shortcomings and provide dopamine where it is needed. Although using human pluripotent stem cells (hPSCs) for treatment of PD is a promising alternative, no consensus in the literature pertains to efficacy concerns of hPSC-based therapy for PD. This systematic review aims to investigate the efficacy of hPSC-derived DA progenitor transplantation to treat PD in preclinical animal models.Methods: This is a systematic review of preclinical studies in animal models of PD. We intend to use the following databases as article sources: MEDLINE (via PubMed), Web of Science, and SCOPUS without any restrictions on language or publication status for all related articles published until the end of 2019. Rescue of motor deficits is defined as the primary outcome, while histological and imaging data comprise the secondary outcomes. Two independent reviewers will select the titles and abstracts, extract data from qualifying studies, and assess the risk of bias by using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. The standardized mean difference (SMD) will be calculated to determine the efficacy of the treatment, with 95% confidence intervals (95% CI). The heterogeneity between studies will be calculated by "I2 inconsistency of values and Cochran's Q statistical test", where I2 > 50% and/or p < 0.10 suggest high heterogeneity. Meta-analyses of random effects will be run when appropriate.Discussion: This study will present an overview of preclinical research on hPSCs and their therapeutic effects in PD animal models. This systematic review will point out the strengths and limitations of studies in the current literature while encouraging the funding of new studies by public health managers and governmental bodies.

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