The Experts below are selected from a list of 25629 Experts worldwide ranked by ideXlab platform
Thomas Hudzik - One of the best experts on this subject based on the ideXlab platform.
-
Drug Tolerance: A Known Unknown in Translational Neuroscience.
Trends in Pharmacological Sciences, 2016Co-Authors: Anton Bespalov, Reinhold Müller, Ana-lucia Relo, Thomas HudzikAbstract:In neuropsychiatric Drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss of efficacy with repeated Drug exposure, is rarely addressed as a potential source of clinical failures. In this review, we argue that preclinical methods of tolerance development may have predictive validity and, therefore, inclusion of studies using repeated Drug exposure early during the Drug discovery and development process should serve to mitigate a proportion of clinical failures. Our analysis indicates that many published preclinical efficacy studies in the neuropsychiatry arena are conducted with Acute Drug Administration only. Furthermore, specifically in the field of schizophrenia, there are several examples where tolerance development may be suspected as a factor contributing to translational failures. These and other examples highlight the need for built-for-purpose tolerance studies to be conducted, regardless of the target interaction mode of the Drugs (i.e., agonist or antagonist, allosteric or orthosteric). We suggest that, for compounds that have failed in clinical studies, preclinical efficacy data sets need to be revisited to estimate the potential impact of tolerance development, one of the most significant known unknowns in the preclinical-to-clinical translation.
Harriet Wit - One of the best experts on this subject based on the ideXlab platform.
-
Effects of Acute Drug Administration on Emotion: a Review of Pharmacological MRI Studies
Current Addiction Reports, 2021Co-Authors: Kathryne Hedger, Leah M. Mayo, Anya K. Bershad, Racheal Madray, Harriet WitAbstract:Purpose of Review Many Drug users claim to use Drugs to cope with negative emotions, which may, in turn, result in persistent emotional blunting or anhedonia even when they are not using Drugs. The purpose of this review is to describe the ways Acute Administration of psychoactive Drugs impacts brain regions during emotion-related tasks, as a first step in understanding how Drugs influence emotion processing in the brain. Recent Findings Drugs have varying effects on neural responses to emotional stimuli. In general, alcohol, analgesics, and psychedelics reduce neural reactivity to negative emotional stimuli in the amygdala and other brain regions. Other Drugs produce mixed effects: Stimulants such as caffeine and modafinil increase brain activation while viewing emotional stimuli, whereas MDMA decreases activation during presentation of negative images. The effects of cannabinoids (cannabidiol and THC) are mixed. There are also inconsistent findings on the associations between neural responses to emotional stimuli and subjective Drug effects. Summary Consistent with the notion that individuals might use Drugs non-medically to diminish the experience of negative emotions, several Drugs of abuse decrease neural responses to negative stimuli in limbic brain regions. These neural actions may underlie the reported “emotional blunting” of Drugs, which may contribute to Drug-seeking behavior. Future work is needed to examine these limbic responses in relation to self-reports of changes in affect, both during Acute Administration and after extended Drug use.
Anton Bespalov - One of the best experts on this subject based on the ideXlab platform.
-
Drug Tolerance: A Known Unknown in Translational Neuroscience.
Trends in Pharmacological Sciences, 2016Co-Authors: Anton Bespalov, Reinhold Müller, Ana-lucia Relo, Thomas HudzikAbstract:In neuropsychiatric Drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss of efficacy with repeated Drug exposure, is rarely addressed as a potential source of clinical failures. In this review, we argue that preclinical methods of tolerance development may have predictive validity and, therefore, inclusion of studies using repeated Drug exposure early during the Drug discovery and development process should serve to mitigate a proportion of clinical failures. Our analysis indicates that many published preclinical efficacy studies in the neuropsychiatry arena are conducted with Acute Drug Administration only. Furthermore, specifically in the field of schizophrenia, there are several examples where tolerance development may be suspected as a factor contributing to translational failures. These and other examples highlight the need for built-for-purpose tolerance studies to be conducted, regardless of the target interaction mode of the Drugs (i.e., agonist or antagonist, allosteric or orthosteric). We suggest that, for compounds that have failed in clinical studies, preclinical efficacy data sets need to be revisited to estimate the potential impact of tolerance development, one of the most significant known unknowns in the preclinical-to-clinical translation.
Reinhold Müller - One of the best experts on this subject based on the ideXlab platform.
-
Drug Tolerance: A Known Unknown in Translational Neuroscience.
Trends in Pharmacological Sciences, 2016Co-Authors: Anton Bespalov, Reinhold Müller, Ana-lucia Relo, Thomas HudzikAbstract:In neuropsychiatric Drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss of efficacy with repeated Drug exposure, is rarely addressed as a potential source of clinical failures. In this review, we argue that preclinical methods of tolerance development may have predictive validity and, therefore, inclusion of studies using repeated Drug exposure early during the Drug discovery and development process should serve to mitigate a proportion of clinical failures. Our analysis indicates that many published preclinical efficacy studies in the neuropsychiatry arena are conducted with Acute Drug Administration only. Furthermore, specifically in the field of schizophrenia, there are several examples where tolerance development may be suspected as a factor contributing to translational failures. These and other examples highlight the need for built-for-purpose tolerance studies to be conducted, regardless of the target interaction mode of the Drugs (i.e., agonist or antagonist, allosteric or orthosteric). We suggest that, for compounds that have failed in clinical studies, preclinical efficacy data sets need to be revisited to estimate the potential impact of tolerance development, one of the most significant known unknowns in the preclinical-to-clinical translation.
Ana-lucia Relo - One of the best experts on this subject based on the ideXlab platform.
-
Drug Tolerance: A Known Unknown in Translational Neuroscience.
Trends in Pharmacological Sciences, 2016Co-Authors: Anton Bespalov, Reinhold Müller, Ana-lucia Relo, Thomas HudzikAbstract:In neuropsychiatric Drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss of efficacy with repeated Drug exposure, is rarely addressed as a potential source of clinical failures. In this review, we argue that preclinical methods of tolerance development may have predictive validity and, therefore, inclusion of studies using repeated Drug exposure early during the Drug discovery and development process should serve to mitigate a proportion of clinical failures. Our analysis indicates that many published preclinical efficacy studies in the neuropsychiatry arena are conducted with Acute Drug Administration only. Furthermore, specifically in the field of schizophrenia, there are several examples where tolerance development may be suspected as a factor contributing to translational failures. These and other examples highlight the need for built-for-purpose tolerance studies to be conducted, regardless of the target interaction mode of the Drugs (i.e., agonist or antagonist, allosteric or orthosteric). We suggest that, for compounds that have failed in clinical studies, preclinical efficacy data sets need to be revisited to estimate the potential impact of tolerance development, one of the most significant known unknowns in the preclinical-to-clinical translation.