Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures

Aviva Gamliel; Gabriel Schreiber; Asher Shainberg

doi:10.1016/0006-2952(87)90590-9

Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures

Aviva Gamliel, Gabriel Schreiber, Asher Shainberg

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2271-2277
Number of pages	7
Journal	Biochemical Pharmacology
Volume	36
Issue number	14
DOIs	https://doi.org/10.1016/0006-2952(87)90590-9
State	Published - 15 Jul 1987
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Pharmacology

Access to Document

10.1016/0006-2952(87)90590-9

Cite this

@article{7fe5db0c27184289ae10208515ba3f5e,

title = "Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures",

abstract = "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.",

author = "Aviva Gamliel and Gabriel Schreiber and Asher Shainberg",

year = "1987",

month = jul,

day = "15",

doi = "10.1016/0006-2952(87)90590-9",

language = "English",

volume = "36",

pages = "2271--2277",

journal = "Biochemical Pharmacology",

issn = "0006-2952",

publisher = "Elsevier Inc.",

number = "14",

}

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

M3 - Article

AN - SCOPUS:0023251827

SN - 0006-2952

VL - 36

SP - 2271

EP - 2277

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 14

ER -

Synergistic inhibition by trifluoperazine and phencyclidine of carbamylcholine-induced cation influx in muscle cultures

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this