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DRUG-MEMBRANE INTERACTIONS Holm Holmsen Department of Biomedicine, UoB. ACTION OF PSYCHIATRIC DRUGS A. The RECEPTOR ANTAGONIST Hypothesis. TRANSMITTER. DRUG. (Blockade). RECEPTOR. RECEPTOR. SIGNAL. The polyphosphoinositide cycle. Tight coupling of phosphorylated metabolites in PPI cycle
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DRUG-MEMBRANE INTERACTIONSHolm Holmsen Department of Biomedicine, UoB
ACTION OF PSYCHIATRIC DRUGS A. The RECEPTOR ANTAGONIST Hypothesis TRANSMITTER DRUG (Blockade) RECEPTOR RECEPTOR SIGNAL
Tight coupling of phosphorylated metabolites in PPI cycle 32P-labelled platelets, [thrombin]var, ,[thrombin]const/[hirudin]var
+CPZ -CPZ -CPZ +CPZ PIP/PA and PIP2/PA relationships with chlorpromazine
Prochlorperazine Trifluoperazine
Quietiapine Haloperidol
Pimozide Clozapine
55 50 45 40 35 30 25 20 15 (ppm) Unilammelar micelles of DPPC/PBPS (70:30) +CPZ (10%) -CPZ
CPZ in 18:0/20:0 PE After simulation, >100 ps Before simulation
CPZ in 18:0/20:4 PE Before simulation After simulation, >100 ps
+ Chlorpromazine does not intercalate in SOPS
+ Chlorpromazine does intercalate in SDPS
ACTION OF PSYCHIATRIC DRUGS B. The MEMBRANE INTERCALATION Hypothesis TRANSMITTER DRUG RECEPTOR RECEPTOR RECEPTOR SIGNAL