Anúncio

Experimental trials of new nootropics

24 de Mar de 2023
Anúncio

Mais conteúdo relacionado

Similar a Experimental trials of new nootropics(20)

Anúncio

Experimental trials of new nootropics

  1. Experimental trials of new nootropics Illia Dorosh, Biotechnology student
  2. Definition • Nootropics – neurometabolic stimulators • Cognitive function (Memory, learning, creativity, motivation, attention) • Resilience to hypoxia and cognitive loads
  3. N06BX Other psychostimulants and nootropics • N06BX01 Meclofenoxate • N06BX02 Pyritinol • N06BX03 Piracetam • N06BX04 Deanol • N06BX05 Fipexide • N06BX06 Citicoline • N06BX07 Oxiracetam • N06BX08 Pirisudanol • N06BX09 Linopirdine • N06BX10 Nizofenone • N06BX11 Aniracetam • N06BX12 Acetylcarnitine • N06BX13 Idebenone • N06BX14 Prolintane • N06BX15 Pipradrol • N06BX16 Pramiracetam • N06BX17 Adrafinil • N06BX18 Vinpocetine • N06BX21 Tetramethylglycoluril • N06BX22 Phenibut Anatomical Therapeutic Chemical (ATC) Classification System
  4. N06BX Other psychostimulants and nootropics • N06BX01 Meclofenoxate • N06BX02 Pyritinol • N06BX03 Piracetam • N06BX04 Deanol • N06BX05 Fipexide • N06BX06 Citicoline • N06BX07 Oxiracetam • N06BX08 Pirisudanol • N06BX09 Linopirdine • N06BX10 Nizofenone • N06BX11 Aniracetam • N06BX12 Acetylcarnitine • N06BX13 Idebenone • N06BX14 Prolintane • N06BX15 Pipradrol • N06BX16 Pramiracetam • N06BX17 Adrafinil • N06BX18 Vinpocetine • N06BX21 Tetramethylglycoluril • N06BX22 Phenibut Anatomical Therapeutic Chemical (ATC) Classification System
  5. History • Piracetam 1964 by Corneliu E. Giurgea
  6. Prescribed for: • Post Hypoxia recovery (stroke) • Alzheimer’s disease patients • Developmental disorders Downregulated expression of nicotinic receptor is observed in
  7. Models • Aplysia sp. (sea slug) 10,000 cells
  8. Time-lapse movie of cultured Xenopus retinal ganglion cell axons. Supplementary Video 2 from Koser, et al. 2016. Nature Neuroscience
  9. Chronic toxicity trials for repeated use Carcinogenic toxicity Mutagenic toxicity LD50 = 5.6 g/kg щурів 20 g/kg мишей Piracetam
  10. 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
  11. ICH guideline M3 1. drug discrimination 2. self-administration of the compound 3. assessment of withdrawal 15. Nonclinical abuse liability
  12. • 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).
  13. Drug wheel
  14. Антидепресанти
  15. 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.
  16. 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.
  17. Effectiveness trials • step down • step through • two compartment test • up-hill avoidance • scopolamine induced test • ischemia induced amnesia memory impairments in basal forebrain • Electroencephalography
  18. Morris water navigation test
  19. Bees
  20. • 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.
  21. Requirements • Pass through the blood brain barrier biopharmaceuticals • B. Subtilis SCK6 масляну кислоту
  22. biopharmaceuticals
  23. • 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
  24. 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)
  25. 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)
  26. Thanks for your attention and memory

Notas do Editor

  1. N 06 BX
  2. N 06 BX
  3. Fc-gamma receptors ну я хочу почати, може не на 20 хвилин
Anúncio