This presentation is a part of my project as a master student, for a course called "Preclinical trials of biopharmaceuticals"
Nootropics are pharmaceuticals, designed to enhance
Cognitive function (Memory, learning, creativity, motivation, attention)
Resilience to hypoxia and cognitive loads
This document discusses various screening models used to evaluate potential antipsychotic drugs. It describes in vitro models that test binding affinity at D1 and D2 dopamine receptors. It also outlines several in vivo models in rodents, including tests that measure catalepsy, foot-shock induced aggression, ability to induce artificial hibernation, and inhibition of behaviors induced by apomorphine (climbing) or amphetamines (stereotypy). The models are used to determine drug doses that produce 50% of the maximum effect to quantify antipsychotic activity and potential.
The current slide focuses on different screening models for neurodegenerative diseases along with a brief description of the diseases where the slides are to the points and brief with detailed evaluation.
This document provides information on screening models used to evaluate antipsychotic agents. It begins with definitions of key terms like antipsychotic drugs, psychosis, and schizophrenia. It then describes types of psychosis and common symptoms. The rest of the document details various in vitro and in vivo models used to screen antipsychotic drugs, including D1/D2 receptor assays, tests of catalepsy in rodents, foot shock-induced aggression, and inhibition of apomorphine climbing in mice. The models aim to reflect the mechanisms of action of antipsychotics and their effects on behaviors related to psychosis.
Principles of neuroreceptor pet imaging_Donald F. Smith dfsmithdfsmith
This document discusses principles of molecular brain imaging in depressive disorders using positron emission tomography (PET). It begins with an overview of the challenges in determining neurochemical involvement in affective disorders. It then covers principles of PET imaging and molecular neuroimaging. Details are provided on the actions of the antidepressant mirtazapine and its enantiomers. The document describes experiments using [11C]mirtazapine PET imaging in pigs and the requirements for human PET. It presents results from initial [11C]mirtazapine PET studies in humans. The goal is to develop evidence-based approaches for neuropsychiatry.
Hans Jürgen-Current situation and future perspetives of antipsychotics in sch...Fundación Ramón Areces
'Psiquiatría: situación actual y perspectivas de futuro'. Este es el título del simposio internacional que organizamos el 16 de junio de 2016 en la Fundación Ramón Areces con las fundaciones Juan José López-Ibor y Lilly en homenaje al doctor Juan José López-Ibor, fallecido en enero de 2015. Durante esta jornada, expertos internacionales abordaráon la profunda crisis que atraviesa la psiquiatría como disciplina científica y especialidad médica. Además, a las 19.00 horas, se presentará el libro con el mismo título del simposio, también en recuerdo del doctor López-Ibor.
Pharmacological screening of Anti-psychotic agentsAbin Joy
This document provides information on screening models used to evaluate potential antipsychotic drugs. It begins with an introduction to psychosis and classification of antipsychotic agents. It then describes several in vivo and in vitro models used for screening including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and D2 receptor binding assays. The in vivo models assess behaviors relevant to antipsychotic effects while the in vitro assays measure binding to specific receptors like the D2 receptor that contribute to antipsychotic mechanisms of action.
This document discusses various screening models used to evaluate potential antipsychotic drugs. It describes in vitro models that test binding affinity at D1 and D2 dopamine receptors. It also outlines several in vivo models in rodents, including tests that measure catalepsy, foot-shock induced aggression, ability to induce artificial hibernation, and inhibition of behaviors induced by apomorphine (climbing) or amphetamines (stereotypy). The models are used to determine drug doses that produce 50% of the maximum effect to quantify antipsychotic activity and potential.
The current slide focuses on different screening models for neurodegenerative diseases along with a brief description of the diseases where the slides are to the points and brief with detailed evaluation.
This document provides information on screening models used to evaluate antipsychotic agents. It begins with definitions of key terms like antipsychotic drugs, psychosis, and schizophrenia. It then describes types of psychosis and common symptoms. The rest of the document details various in vitro and in vivo models used to screen antipsychotic drugs, including D1/D2 receptor assays, tests of catalepsy in rodents, foot shock-induced aggression, and inhibition of apomorphine climbing in mice. The models aim to reflect the mechanisms of action of antipsychotics and their effects on behaviors related to psychosis.
Principles of neuroreceptor pet imaging_Donald F. Smith dfsmithdfsmith
This document discusses principles of molecular brain imaging in depressive disorders using positron emission tomography (PET). It begins with an overview of the challenges in determining neurochemical involvement in affective disorders. It then covers principles of PET imaging and molecular neuroimaging. Details are provided on the actions of the antidepressant mirtazapine and its enantiomers. The document describes experiments using [11C]mirtazapine PET imaging in pigs and the requirements for human PET. It presents results from initial [11C]mirtazapine PET studies in humans. The goal is to develop evidence-based approaches for neuropsychiatry.
Hans Jürgen-Current situation and future perspetives of antipsychotics in sch...Fundación Ramón Areces
'Psiquiatría: situación actual y perspectivas de futuro'. Este es el título del simposio internacional que organizamos el 16 de junio de 2016 en la Fundación Ramón Areces con las fundaciones Juan José López-Ibor y Lilly en homenaje al doctor Juan José López-Ibor, fallecido en enero de 2015. Durante esta jornada, expertos internacionales abordaráon la profunda crisis que atraviesa la psiquiatría como disciplina científica y especialidad médica. Además, a las 19.00 horas, se presentará el libro con el mismo título del simposio, también en recuerdo del doctor López-Ibor.
Pharmacological screening of Anti-psychotic agentsAbin Joy
This document provides information on screening models used to evaluate potential antipsychotic drugs. It begins with an introduction to psychosis and classification of antipsychotic agents. It then describes several in vivo and in vitro models used for screening including tests measuring catalepsy in rodents, inhibition of amphetamine-induced stereotypy, and D2 receptor binding assays. The in vivo models assess behaviors relevant to antipsychotic effects while the in vitro assays measure binding to specific receptors like the D2 receptor that contribute to antipsychotic mechanisms of action.
1. The study investigated the role of the central dopaminergic system in the analgesic action of paracetamol using rodent pain models.
2. It found that paracetamol's analgesic activity increased when combined with drugs that increase dopamine levels and decreased when combined with a dopamine blocker.
3. Brain dopamine levels were higher in mice treated with paracetamol plus drugs increasing dopamine, and lower with a dopamine-decreasing drug. This suggests modulation of the dopaminergic system contributes to paracetamol's analgesic effects.
This document discusses various in vitro and in vivo models for screening antipsychotic drugs. It begins by providing background on schizophrenia and antipsychotic drugs. It then describes two important in vitro models - the D1 receptor assay using 3H-SCH 23390 binding and the D2 receptor assay using 3H spiroperidol binding. Both assays are used to determine binding affinity of test compounds to dopamine receptors. Three key in vivo models are also outlined - the open field test to evaluate motor activity, the rota rod test to assess motor coordination, and the grip strength test to measure muscular strength. The document provides details on the procedures and evaluation of these screening models.
Neurotransmitters are chemical messengers that transmit signals between neurons. The document discusses several major neurotransmitters - acetylcholine, serotonin, histamine, glutamate, GABA, glycine, aspartate, dopamine, and norepinephrine. It describes the receptors they act on, whether they are excitatory or inhibitory, their roles in various body systems and mental processes, and how imbalances can relate to conditions like depression, anxiety, and Parkinson's disease. The document also mentions neuropeptides like endorphins that modulate pain, and recent research exploring links between brain and urinary neurotransmitter levels.
This document discusses drug addiction from a neurobiological perspective. It begins with definitions of addiction and explanations for why it is considered a disease. It then covers topics like the neurobiology of reward systems in the brain, dopaminergic pathways involved in addiction like the mesolimbic pathway, and the role of dopamine in drug addiction. It classifies drugs of abuse based on their neuropharmacological targets and mechanisms of action. Specific drugs discussed include opioids, cannabinoids, hallucinogens, and nicotine. Withdrawal symptoms and treatment approaches for certain drug addictions are also summarized.
This document summarizes a seminar presentation on screening methods for antidepressant drugs. The presentation covers in vivo and in vitro methods for evaluating potential antidepressant drugs in preclinical studies. Some key in vivo methods discussed include the forced swim test, tail suspension test, and reserpine-induced hypothermia in rats. Important in vitro screening assays mentioned are those examining inhibition of monoamine reuptake (norepinephrine and serotonin) in rat brain synaptosomes and inhibition of monoamine oxidase enzyme activity. A conclusion states that while no single preclinical model fully captures human depression, the forced swim test and tail suspension test are widely used initial screens for assessing antidepressant activity.
In this slide we enlighten the Drug Discovery and Development with the different approaches of drug development like Pharmacological, Toxicological, Drug Characterization, IND Application and Dosage Form Approach.
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptxGautamSosa
Neurodegenerative diseases are conditions where nerve cells in the brain and peripheral nervous system gradually degenerate and die, leading to cognitive decline, movement disorders, and sometimes death. Examples include Alzheimer's, Parkinson's, multiple sclerosis and Huntington's disease. Treatment focuses on symptom management, as there are currently no cures for these conditions. Efficacy evaluation of any drug for Alzheimer's, Parkinson's, and multiple sclerosis in in-vivo animal studies, first step is to learn the in-vivo screening model of particular disease.
This document discusses preclinical screening models used to test for anti-psychotic activity. It begins with an introduction and classifications of antipsychotics. It then describes various screening methods including behavioral tests in rodents and tests based on pharmacologic antagonism. Several experiments are outlined testing drugs in models of catalepsy in rats and inhibition of amphetamine-induced behaviors. Future approaches discussed include using models involving phencyclidine and developmental models. The screening methods are used to compare new drugs to known effective antipsychotics and provide insight into mechanisms of action.
Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. The symptoms of schizophrenia are classified into positive, negative and cognitive symptoms. New receptor targets and drugs have being evaluated for addressing the multifaceted syndrome of schizophrenia.
is a chronic and disabling mental illness affecting millions of people worldwide. The symptoms of schizophrenia are classified into positive, negative and cognitive symptoms. New receptor targets and drugs have being evaluated for addressing the multifaceted syndrome of schizophrenia.
This study investigated differences in microRNA expression between two rat strains with different responses to drugs. Previous research found differences in miR-26a and miR-484 expression in the nucleus accumbens of high-responder and low-responder rats after cocaine exposure, using qPCR. The current study used in situ hybridization to validate these findings and identify the neuroanatomical locations of miRNA expression. Results showed downregulation of miR-26a in the nucleus accumbens core of low-responder rats exposed to cocaine compared to saline, consistent with prior qPCR results. However, results for miR-484 were not statistically significant. This study provides neuroanatomical information on miRNA expression differences between rat strains in response
The document discusses the process of new drug development, which involves drug discovery through approaches like exploring natural sources, rational design, and combinatorial chemistry. Drugs then undergo preclinical testing in animals to evaluate safety and efficacy. If promising, drugs enter clinical trials in four phases with humans to further assess safety, efficacy, dosing, and side effects. Successful drugs are approved by regulatory agencies and undergo post-marketing surveillance to monitor long-term effects. The overall process from discovery to marketing can take over 10 years and cost over $500 million.
Preclinical drug discovery and developmentsamthamby79
This document provides an overview of preclinical drug discovery and development processes. It discusses rational drug design, screening approaches, molecular modification of lead compounds, pharmacokinetic and toxicology studies in animal models, and regulatory requirements for data on a drug's primary pharmacology, secondary effects, and interactions prior to clinical trials. The goal of preclinical research is to obtain sufficient safety and efficacy data on new chemical entities to justify testing in humans.
Translational Neuroscience Approach in psychiatry..pptxkrishray616
Translational neuroscience aims to bridge the gap between fundamental scientific research and clinical applications to treat neurological disorders. It focuses on applying discoveries from preclinical research, like animal and cell models, to develop new therapies. Translational neuroscience research occurs across both wet labs, which use experimental techniques, and dry labs, which analyze data through computational methods. The goal is to more quickly translate basic scientific findings into clinical applications that can improve patient outcomes. Identifying biomarkers that indicate disease mechanisms or predict treatment responses is an important part of translational research efforts.
Preclinical Screening for Neurodegenerative Disease (Parkinsonism)Drx Burade
This file includes the general introduction of Parkinson's, sign and symptoms of Parkinson's, treatment of Parkinson's and the main content that is the Preclinical Screening models for Neurodegenerative disease like Parkinson's
The pharmacology of proteins and peptidesOdetteHeyneke
The document provides an overview of the pharmacology of proteins and peptides. It discusses the historical perspective of using peptides as therapeutic drugs, beginning in the 1970s. It compares neuropeptides to conventional neurotransmitters in their biosynthesis, storage, and mechanisms of action. The document outlines different classes of biologically active peptides and techniques used to identify, isolate, and characterize peptides. It also discusses using peptides and proteins as therapeutic drugs, including peptide agonists and antagonists that target endogenous receptors.
Newer Trends and Recent Advances in Parasympathomimetics and parasympatholyticsShubham Marbade
It describes about newer trends and Recent Advances in Parasympathomimetics and parasympatholytics and their mechanism of actions
by Shubham marbade
Department of Pharmacology
1. The study investigated the role of the central dopaminergic system in the analgesic action of paracetamol using rodent pain models.
2. It found that paracetamol's analgesic activity increased when combined with drugs that increase dopamine levels and decreased when combined with a dopamine blocker.
3. Brain dopamine levels were higher in mice treated with paracetamol plus drugs increasing dopamine, and lower with a dopamine-decreasing drug. This suggests modulation of the dopaminergic system contributes to paracetamol's analgesic effects.
This document discusses various in vitro and in vivo models for screening antipsychotic drugs. It begins by providing background on schizophrenia and antipsychotic drugs. It then describes two important in vitro models - the D1 receptor assay using 3H-SCH 23390 binding and the D2 receptor assay using 3H spiroperidol binding. Both assays are used to determine binding affinity of test compounds to dopamine receptors. Three key in vivo models are also outlined - the open field test to evaluate motor activity, the rota rod test to assess motor coordination, and the grip strength test to measure muscular strength. The document provides details on the procedures and evaluation of these screening models.
Neurotransmitters are chemical messengers that transmit signals between neurons. The document discusses several major neurotransmitters - acetylcholine, serotonin, histamine, glutamate, GABA, glycine, aspartate, dopamine, and norepinephrine. It describes the receptors they act on, whether they are excitatory or inhibitory, their roles in various body systems and mental processes, and how imbalances can relate to conditions like depression, anxiety, and Parkinson's disease. The document also mentions neuropeptides like endorphins that modulate pain, and recent research exploring links between brain and urinary neurotransmitter levels.
This document discusses drug addiction from a neurobiological perspective. It begins with definitions of addiction and explanations for why it is considered a disease. It then covers topics like the neurobiology of reward systems in the brain, dopaminergic pathways involved in addiction like the mesolimbic pathway, and the role of dopamine in drug addiction. It classifies drugs of abuse based on their neuropharmacological targets and mechanisms of action. Specific drugs discussed include opioids, cannabinoids, hallucinogens, and nicotine. Withdrawal symptoms and treatment approaches for certain drug addictions are also summarized.
This document summarizes a seminar presentation on screening methods for antidepressant drugs. The presentation covers in vivo and in vitro methods for evaluating potential antidepressant drugs in preclinical studies. Some key in vivo methods discussed include the forced swim test, tail suspension test, and reserpine-induced hypothermia in rats. Important in vitro screening assays mentioned are those examining inhibition of monoamine reuptake (norepinephrine and serotonin) in rat brain synaptosomes and inhibition of monoamine oxidase enzyme activity. A conclusion states that while no single preclinical model fully captures human depression, the forced swim test and tail suspension test are widely used initial screens for assessing antidepressant activity.
In this slide we enlighten the Drug Discovery and Development with the different approaches of drug development like Pharmacological, Toxicological, Drug Characterization, IND Application and Dosage Form Approach.
IN-VIVO SCREENING METHODS FOR NEURODEGENERATIVE DISEASE.pptxGautamSosa
Neurodegenerative diseases are conditions where nerve cells in the brain and peripheral nervous system gradually degenerate and die, leading to cognitive decline, movement disorders, and sometimes death. Examples include Alzheimer's, Parkinson's, multiple sclerosis and Huntington's disease. Treatment focuses on symptom management, as there are currently no cures for these conditions. Efficacy evaluation of any drug for Alzheimer's, Parkinson's, and multiple sclerosis in in-vivo animal studies, first step is to learn the in-vivo screening model of particular disease.
This document discusses preclinical screening models used to test for anti-psychotic activity. It begins with an introduction and classifications of antipsychotics. It then describes various screening methods including behavioral tests in rodents and tests based on pharmacologic antagonism. Several experiments are outlined testing drugs in models of catalepsy in rats and inhibition of amphetamine-induced behaviors. Future approaches discussed include using models involving phencyclidine and developmental models. The screening methods are used to compare new drugs to known effective antipsychotics and provide insight into mechanisms of action.
Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. The symptoms of schizophrenia are classified into positive, negative and cognitive symptoms. New receptor targets and drugs have being evaluated for addressing the multifaceted syndrome of schizophrenia.
is a chronic and disabling mental illness affecting millions of people worldwide. The symptoms of schizophrenia are classified into positive, negative and cognitive symptoms. New receptor targets and drugs have being evaluated for addressing the multifaceted syndrome of schizophrenia.
This study investigated differences in microRNA expression between two rat strains with different responses to drugs. Previous research found differences in miR-26a and miR-484 expression in the nucleus accumbens of high-responder and low-responder rats after cocaine exposure, using qPCR. The current study used in situ hybridization to validate these findings and identify the neuroanatomical locations of miRNA expression. Results showed downregulation of miR-26a in the nucleus accumbens core of low-responder rats exposed to cocaine compared to saline, consistent with prior qPCR results. However, results for miR-484 were not statistically significant. This study provides neuroanatomical information on miRNA expression differences between rat strains in response
The document discusses the process of new drug development, which involves drug discovery through approaches like exploring natural sources, rational design, and combinatorial chemistry. Drugs then undergo preclinical testing in animals to evaluate safety and efficacy. If promising, drugs enter clinical trials in four phases with humans to further assess safety, efficacy, dosing, and side effects. Successful drugs are approved by regulatory agencies and undergo post-marketing surveillance to monitor long-term effects. The overall process from discovery to marketing can take over 10 years and cost over $500 million.
Preclinical drug discovery and developmentsamthamby79
This document provides an overview of preclinical drug discovery and development processes. It discusses rational drug design, screening approaches, molecular modification of lead compounds, pharmacokinetic and toxicology studies in animal models, and regulatory requirements for data on a drug's primary pharmacology, secondary effects, and interactions prior to clinical trials. The goal of preclinical research is to obtain sufficient safety and efficacy data on new chemical entities to justify testing in humans.
Translational Neuroscience Approach in psychiatry..pptxkrishray616
Translational neuroscience aims to bridge the gap between fundamental scientific research and clinical applications to treat neurological disorders. It focuses on applying discoveries from preclinical research, like animal and cell models, to develop new therapies. Translational neuroscience research occurs across both wet labs, which use experimental techniques, and dry labs, which analyze data through computational methods. The goal is to more quickly translate basic scientific findings into clinical applications that can improve patient outcomes. Identifying biomarkers that indicate disease mechanisms or predict treatment responses is an important part of translational research efforts.
Preclinical Screening for Neurodegenerative Disease (Parkinsonism)Drx Burade
This file includes the general introduction of Parkinson's, sign and symptoms of Parkinson's, treatment of Parkinson's and the main content that is the Preclinical Screening models for Neurodegenerative disease like Parkinson's
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The document provides an overview of the pharmacology of proteins and peptides. It discusses the historical perspective of using peptides as therapeutic drugs, beginning in the 1970s. It compares neuropeptides to conventional neurotransmitters in their biosynthesis, storage, and mechanisms of action. The document outlines different classes of biologically active peptides and techniques used to identify, isolate, and characterize peptides. It also discusses using peptides and proteins as therapeutic drugs, including peptide agonists and antagonists that target endogenous receptors.
Newer Trends and Recent Advances in Parasympathomimetics and parasympatholyticsShubham Marbade
It describes about newer trends and Recent Advances in Parasympathomimetics and parasympatholytics and their mechanism of actions
by Shubham marbade
Department of Pharmacology
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12. Time-lapse movie of cultured Xenopus retinal
ganglion cell axons. Supplementary Video 2
from Koser, et al. 2016. Nature Neuroscience
13.
14.
15.
16. Chronic toxicity trials for repeated use
Carcinogenic toxicity
Mutagenic toxicity
LD50 =
5.6 g/kg щурів
20 g/kg мишей
Piracetam
17. Abuse potential evaluation
Profile of the receptor binding in vivo
Sales rules (Prescription or over the counter)
Local recommendations FDA, EMA
New CNS actions mechanisms
additional precilinical trials
18. ICH guideline M3
1. drug discrimination
2. self-administration of the compound
3. assessment of withdrawal
15. Nonclinical abuse liability
19. • If a substance shows the signals, similar to
known models of abuse or a new mechanism
of addiction, additional nonclinial trials are
needed in parallel (for examphle, phase III).
23. operant conditioning methods
• innovative studies of Barry
(1968) and Morrison and Stephenson (1969),
two-bar operant conditioning techniques
• relative response rates, rather than upon
absolute response rates
• one of the major problems in behavioural
pharmacology, the distinction between
specific drug effects and general excitatory or
sedative effects, is very largely avoided.
24.
25. Drug discrimination typically involves training an
animal to produce a particular response in a given
drug state for a food reinforcer and to produce a
different response for the same food reinforcer in
the placebo or nondrug state. The interoceptive cue
state that is produced by the drug controls behavior
as a discriminative stimulus or cue that informs the
animal to make the appropriate response to gain
reinforcement. The choice of the response that
follows the administration of an unknown test
compound can provide valuable information about
the similarity of that drug's interoceptive cue
properties to those of the training drug.
26.
27. Effectiveness trials
• step down
• step through
• two compartment test
• up-hill avoidance
• scopolamine induced test
• ischemia induced amnesia memory
impairments in basal forebrain
• Electroencephalography
31. • Радіолігандні дослідження краще виконувати, маючи
мічену речовину, що досліджується [24]. Однак її синтез
стає економічно доцільним на етапі клінічних
досліджень. На доклінічному етапі вивчають вплив
неміченої сполуки на зв'язування з синаптосомами
мозку специфічних мічених лігандів: [3Н]-
флунітразепаму (ліганд бензодіазепінових рецепторів),
[3Н]- спіперону (ліганд D2 дофамінових і 5-НТ2
рецепторів), [3Н]-іпсапірону (ліганд 5-НТІА рецепторів).
Вивчають вплив ФЗ на зв'язування цих мічених лігандів
мембранами різних структур мозку - стріатума,
гіпокампа, фронтальної кори. У дослідах з міченим
спіпероном стріатум розглядають як джерело D2, а кору
- як джерело 5-НТ2 рецепторів.
37. • Immediately after decapitation, the necessary brain structures are isolated
on ice from the brains of several rats, weighed and homogenized in a 32-
fold volume of 50 mM TRIS buffer (pH = 7.4) in a glass-Teflon homogenizer
on ice. The homogenate is centrifuged at 30,000 g for 20 minutes. The
resulting precipitate is resuspended in the same buffer and centrifuged
again. The final sediment is dissolved in the same buffer so that the
protein content in the sample is 0.15 mg. The binding of [ 3H]-
flunitrazepam (0.125 nM) is studied with a total incubation volume of 500
μl. Nonspecific binding is determined in the presence of 10 μM
flunitrazepam. The substance under investigation is used in several
concentrations (from 1010 to 10"4 M). After 60 minutes of incubation (on
ice), the reaction in all test tubes is stopped by rapid filtration through
glass fiber filters GF/B (Whatman). The filters are washed three times
cooled buffer. A day before measuring radioactivity, filters are placed in 5
ml of scintillation liquid (ACS). Radioactivity is measured using a liquid
scintillation counter and IC50 is determined - the concentration of a
substance that inhibits the specific binding of [3H]-flunitrazepam by 50%
[25] Under similar conditions, the membrane suspension is incubated with
labeled spiperone (final concentration 0.1-0.25 nM) or [3H]-ipsapyrone (2
nM) in the absence and presence of various concentrations of the
substance under investigation. that is being studied are measured in
nanomolar concentrations, the conclusion about the high affinity of the
compound to the receptors corresponding to the labeled ligand is correct
38. References
• Evaluation of the specific pharmacological activity of medicinal
products
• Komissarov I.V., Abramets I.I. New look at the molecular
mechanisms of action of psychopharmacological agents//Arch.
wedge, and experiment. Medicine .- 1993.- Т.2, №1.- С.6-12.
• ICH guideline M3(R2) on non-clinical safety studies for the conduct
of human clinical trials and marketing authorisation for
pharmaceuticals
• Pardridge WM. Re-engineering biopharmaceuticals for delivery to
brain with molecular Trojan horses. Bioconjug Chem. 2008
Jul;19(7):1327-38. doi: 10.1021/bc800148t. Epub 2008 Jun 12.
PMID: 18547095.
• Hesp, Casper & Smith, Ryan & Parr, Thomas & Allen, Micah &
Friston, Karl & Ramstead, Maxwell. (2019). Deeply Felt Affect: The
Emergence of Valence in Deep Active Inference.
10.31234/osf.io/62pfd.
• Arish, M. R., Tong Michelle, T. T. Making “Good” Choices: Social
Isolation in Mice Exacerbates the Effects of Chronic Stress on
Decision Making. Frontiers in Behavioral Neuroscience, 14(81)
39. References II
• Establishing Natural Nootropics: Recent Molecular
Enhancement Influenced by Natural Nootropic
https://doi.org/10.1155/2016/4391375
Evidence-Based Complementary and Alternative
Medicine
Hindawi Publishing Corporation
• Вивчення здатності до навчання та пам'яті:
формування умовних рефлексів як з позитивним,
так і з негативним підкріпленням та збереження
отриманих навичок (Я. Бурені та співавт., 1991).
• (Вікторов О.П., 2011)