TY - JOUR
T1 - Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures
AU - Gamliel, Aviva
AU - Schreiber, Gabriel
AU - Shainberg, Asher
PY - 1987/7/15
Y1 - 1987/7/15
N2 - The effect of trifluoperazine (TFP) and phencyclidine (PCP) on acetylcholine receptor (AChR) function was studied in rat myotubes differentiated in vitro. While both drugs exerted an inhibitory effect on carbamylcholine (CCh)-induced Na+ or Ca2+ flux (I50 = 5-9 μM), α-bungarotoxin (α-Bgt) binding was not affected. The inhibitory effect of both drugs was independent of CCh concentration. The mutual inhibitory effect of TFP and PCP on Ca2+ influx was analyzed using three alternative models of interaction between the two drugs: competitive, additive and synergistic inhibition models. Our results are in accord with a synergistic interaction between the drugs probably not through desensitization. This synergistic interaction between the drugs provides a biochemical rationale to the phenothiazine contraindication in the treatment of PCP psychosis.
AB - The effect of trifluoperazine (TFP) and phencyclidine (PCP) on acetylcholine receptor (AChR) function was studied in rat myotubes differentiated in vitro. While both drugs exerted an inhibitory effect on carbamylcholine (CCh)-induced Na+ or Ca2+ flux (I50 = 5-9 μM), α-bungarotoxin (α-Bgt) binding was not affected. The inhibitory effect of both drugs was independent of CCh concentration. The mutual inhibitory effect of TFP and PCP on Ca2+ influx was analyzed using three alternative models of interaction between the two drugs: competitive, additive and synergistic inhibition models. Our results are in accord with a synergistic interaction between the drugs probably not through desensitization. This synergistic interaction between the drugs provides a biochemical rationale to the phenothiazine contraindication in the treatment of PCP psychosis.
UR - http://www.scopus.com/inward/record.url?scp=0023251827&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(87)90590-9
DO - 10.1016/0006-2952(87)90590-9
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C2 - 3606641
AN - SCOPUS:0023251827
SN - 0006-2952
VL - 36
SP - 2271
EP - 2277
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 14
ER -