02025nas a2200193   4500008004100000022001400041245011400055210006900169260001200238300001400250490000700264520141800271653001201689100002301701700002101724700001501745700002401760856004701784       1983                        eng d  a0027-842400aElectrophysiological and biochemical studies on enhancement of desensitization by phenothiazine neuroleptics.0 aElectrophysiological and biochemical studies on enhancement of d  c01/1983  a310–3140 v803 aThe actions of the phenothiazines chlorpromazine, prochlorperazine, and trifluoperazine were studied on the acetylcholine receptor-ionic channel complex of frog and rat skeletal muscle and of Torpedo californica to determine their role in pharmacological desensitization and their interactions with different states of the receptor-ionic channel complex. The phenothiazines depressed the peak amplitude of spontaneous and evoked endplate currents while having negligible effect on the decay time constants. Mean channel lifetime and single channel conductance were not altered by these drugs. They also produced a frequency-dependent depression of the peak amplitude of endplate potentials evoked by repetitive microiontophoresis at the extrajunctional region. In addition, these drugs enhanced the ability of carbamoylcholine to displace 125I-labeled alpha-bungarotoxin from receptor-rich membrane preparations of T. californica when used in concentrations that had no effect on 125I-labeled alpha-bungarotoxin binding alone (10 microM). Similarly, the phenothiazines inhibited the binding of tritiated ionic channel ligands, such as phencyclidine and perhydrohistrionicotoxin, a process also enhanced by the presence of carbamoylcholine. These data suggest that the phenothiazines augment agonist-induced desensitization primarily by interacting with the receptor-ionic channel complex prior to channel opening.10aTorpedo1 aCarp, Jonathan, S.1 aAronstam, R., S.1 aWitkop, B.1 aAlbuquerque, E., X.  uhttp://www.ncbi.nlm.nih.gov/pubmed/6130531