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Chuang CC, Marrazzi AS. 
“Analysis Of Drug Block Of LSD/5HT/GABA By Monitoring Neuronal Membrane Changes”. 
Fed. Proc.. 1973;32(3):303 Abs..
We have previously shown that 5HT and LSD are potent cerebral synaptic inhibitors and that they are blocked by CPZ and strychnine; and that GABA inhibits and is blocked by Strych. but not CPZ. Continuous intracellular monitoring of membrane changes in pyramidal, pericruciate cortex cells (flaxedilized cats) establishes that closo-arterially injected 5HT, LSD and CPZ act in a qualitatively identical fashion, with 5HT being most active, LSD less and CPZ very much less. In all three the concomitant changes are reduced or stopped firing hyperpolarization, reduced EPSPs (evoked by V. L. Thalamic stimulation), appearance and increase of IPSPs and decreased conductance. Thus, CPZ appears to block by substituting at, evidently, the identical membrane site an identical but much weaker action for 5HT or LSD, demonstrating competitive inhibition in terms of critical membrane changes. CPZ local anesthesia is excluded as a factor since xylocaine, enough to reduce firing, did not reproduce the other changes. Strych. gives all the membrane changes. GABA membrane changes are similar except for an increased conductance. Strych. blocking all, is less specific and blocks GABA, presumably, largely by reducing inhibition in another contributing channel rather than the high conductance one. The data provide a cellular basis for a specific, competitive, and differential inhibition (CPZ), and far a less specific block (Strych.).
Notes # : Abst., No. 494
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