Modification of GABA-mediated depolarization of the cat ganglion by pentobarbital and two benzodiazepines

Schlosser, Walter; Franco, S.

doi:10.1016/0028-3908(79)90145-x

Cited by 29 publications

(7 citation statements)

References 31 publications

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“…The only difference between these barbiturates was a five fold lower potency of phenobarbitone. Phenytoin did not affect the actions of picrotoxin in agreement with the present results but in contrast, the benzodiazepine chlordiazepoxide was also without effect (Nicoll & Wojtowicz, 1980 (Macdonald & Barker, 1979;Schlosser & Franco, 1979). However, the underlying mechanisms of potentiation may be different, since inhibitory processes thought to be mediated by GABA were enhanced by phenobarbitone in vivo in a distinctly different way from the enhancement by benzodiazepines (Polc & Haefely, 1976).…”

Section: Discussionsupporting

confidence: 89%

“…Evidence from several laboratories indicates that the responses of neurones to ly-aminobutyric acid (GABA) can be potentiated by a variety of depressant and anticonvulsant drugs, including barbiturates (Nicoll, 1975;Ransom & Barker, 1976;Barker & Ransom, 1978;Brown & Constanti, 1978;Schlosser & Franco, 1979), benzodiazepines (Choi, Farb & Fischbach, 1977;Macdonald & Barker, 1978a, 1979Okamoto & Sakai, 1979) and sometimes phenytoin (Ayala, Johnston, Lin & Dichter, 1977;Adams & Banks, 1980;Nicoll & Wojtowicz, 1980). The basis of this effect for the barbiturates and phenytoin seems likely to be a prolongation of the open time of the chloride channels operated by GABA (Barker & McBurney, 1979;Mathers & Barker, 1980;Adams & Banks, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Distinction Between the Effects of Barbiturates, Benzodiazepines and Phenytoin on Responses to Γ‐aminobutyric Acid Receptor Activation and Antagonism by Bicuculline and Picrotoxin

Simmonds

1981

British J Pharmacology

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1 Interactions of depressant and anticonvulsant drugs with the neuronal y-aminobutyric acid (GABA) receptor+effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Distinction Between the Effects of Barbiturates, Benzodiazepines and Phenytoin on Responses to Γ‐aminobutyric Acid Receptor Activation and Antagonism by Bicuculline and Picrotoxin

Simmonds

1981

British J Pharmacology

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“…Transmission block, but not depolarization, was antagonized by the GABA antagonists, bicuculline and picrotoxin. In doses below 3 x 10-7 mol, flurazepam and midazolam increased the amplitude and duration of ganglionic depolarization induced by GABA (SCHLOSSER and FRANCO, 1979 a); higher doses decreased the amplitude but still prolonged the duration of GAB A-induced depolarization (SCHLOS-SER et aI., 1977;SCHLOSSER and FRANCO, 1979a). An inconsistent and extremely weak potentiation of GAB A-induced depolarization ofthe superfused isolated rat superior cervical ganglion was observed with 1O-6 -10-4 mol·l-1 chlordiazepoxide (STRAUGHAN, 1977;DRAY, 1978), diazepam, flurazepam, andnitrazepam (STRAUGHAN 1977).…”

Section: Synaptic Transmission In Sympathetic Gangliamentioning

confidence: 96%

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

Haefely¹,

Pieri²,

Polc³

et al. 1981

Handbook of Experimental Pharmacology

114

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“…Picrotoxin antagonizes GABA and its analogue muscimol in a manner that is not competitive (Simmonds, 1980), while benzodiazepines potentiate responses to GABA and muscimol (Choi, Farb & Fischbach, 1977;MacDonald & Barker, 1978;Simmonds, 1981). Barbiturates also have a modulatory influence on this complex that results in potentiations of GABA and muscimol (Nicoll, 1975;Ransom & Barker, 1976;Barker & Ransom, 1978;Brown & Constanti, 1978;Schlosser & Franco, 1979;Simmonds, 1981). In addition, evidence has been obtained which suggests that both barbiturates and benzodiazepines can reduce the potency of picrotoxin as an antagonist of muscimol (Simmonds, 1981).…”

Section: Introductionmentioning

confidence: 99%

Two distinct interactions of barbiturates and chlormethiazole with the GABA_A receptor complex in rat cuneate nucleus in vitro

Harrison

Simmonds

1983

British J Pharmacology

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1Some pharmacological properties of the GABAA receptor complex in the rat cuneate nucleus slice have been assessed from depolarization responses to the y-aminobutyric acid (GABA) analogue muscimol and antagonism of the responses by bicuculline and picrotoxin. 2 Responses to muscimol were potentiated by the following drugs, in descending order of potency with regard to the concentrations required in the Krebs medium:Primidone and phenylethylmalonamide were inactive. Calculation of the concentrations likely to be present in membrane lipids for equal potentiations of muscimol revealed little difference between quinalbarbitone, pentobarbitone, phenobarbitone and barbitone. 3 The effect of picrotoxin as a muscimol antagonist was selectively reduced only by DMBB, chlormethiazole, phenobarbitone and ( -)-methylphenobarbitone in concentrations that caused only a modest potentiation of muscimol. 4 It is suggested that a specific site of action in the GABAA receptor complex is involved in the reduction of picrotoxin effect and that this may be relevant to the anticonvulsant properties of chlormethiazole, phenobarbitone and ( -)-methylphenobarbitone. The potentiation of muscimol by chlormethiazole and the barbiturates in general involves a distinctly different site that is less selective and this may underlie the hypnotic properties of these drugs.

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Modification of GABA-mediated depolarization of the cat ganglion by pentobarbital and two benzodiazepines

Cited by 29 publications

References 31 publications

Distinction Between the Effects of Barbiturates, Benzodiazepines and Phenytoin on Responses to Γ‐aminobutyric Acid Receptor Activation and Antagonism by Bicuculline and Picrotoxin

Distinction Between the Effects of Barbiturates, Benzodiazepines and Phenytoin on Responses to Γ‐aminobutyric Acid Receptor Activation and Antagonism by Bicuculline and Picrotoxin

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

Two distinct interactions of barbiturates and chlormethiazole with the GABA_A receptor complex in rat cuneate nucleus in vitro

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Modification of GABA-mediated depolarization of the cat ganglion by pentobarbital and two benzodiazepines

Cited by 29 publications

References 31 publications

Distinction Between the Effects of Barbiturates, Benzodiazepines and Phenytoin on Responses to Γ‐aminobutyric Acid Receptor Activation and Antagonism by Bicuculline and Picrotoxin

Distinction Between the Effects of Barbiturates, Benzodiazepines and Phenytoin on Responses to Γ‐aminobutyric Acid Receptor Activation and Antagonism by Bicuculline and Picrotoxin

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro

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Two distinct interactions of barbiturates and chlormethiazole with the GABA_A receptor complex in rat cuneate nucleus in vitro