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Drug-Membrane Interactions: Understanding the Action of Psychiatric Drugs on Receptors

Delve into the dynamics of psychiatric drugs acting on receptors through membrane interactions. Explore the receptor antagonist hypothesis and transmitter drug blockade mechanism, examining the tight coupling of metabolites in the polyphosphoinositide cycle. Gain insights into the intercalation of drugs like chlorpromazine in membranes with simulations and micelle studies. Uncover the significance of drug-membrane interactions in psychiatric pharmacology.

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Drug-Membrane Interactions: Understanding the Action of Psychiatric Drugs on Receptors

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  1. DRUG-MEMBRANE INTERACTIONSHolm Holmsen Department of Biomedicine, UoB

  2. ACTION OF PSYCHIATRIC DRUGS A. The RECEPTOR ANTAGONIST Hypothesis TRANSMITTER DRUG (Blockade) RECEPTOR RECEPTOR SIGNAL

  3. The polyphosphoinositide cycle

  4. Tight coupling of phosphorylated metabolites in PPI cycle 32P-labelled platelets, [thrombin]var, ,[thrombin]const/[hirudin]var

  5. +CPZ -CPZ -CPZ +CPZ PIP/PA and PIP2/PA relationships with chlorpromazine

  6. Prochlorperazine Trifluoperazine

  7. Quietiapine Haloperidol

  8. Pimozide Clozapine

  9. 55 50 45 40 35 30 25 20 15 (ppm) Unilammelar micelles of DPPC/PBPS (70:30) +CPZ (10%) -CPZ

  10. CPZ in 18:0/20:0 PE After simulation, >100 ps Before simulation

  11. CPZ in 18:0/20:4 PE Before simulation After simulation, >100 ps

  12. + Chlorpromazine does not intercalate in SOPS

  13. + Chlorpromazine does intercalate in SDPS

  14. ACTION OF PSYCHIATRIC DRUGS B. The MEMBRANE INTERCALATION Hypothesis TRANSMITTER DRUG RECEPTOR RECEPTOR RECEPTOR SIGNAL

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