Effects of picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression

M. Billingsley, A. Suria, J. Williams

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Intravenous administration of chlordiazepoxide (CDP) caused respiratory depression in both rats and cats. The maximally tolerated dose of CDP was found to be 165 ± 15 mg/kg, i.v., in rats. Pretreatment with picrotoxin (1.5 mg/kg) or naloxone (20 mg/kg, i.v.) significantly increased the maximally tolerated dose of CDP to 330 ± 40 mg/kg, i.v., and 270 ± 35 mg/kg, i.v., respectively. The protective effects of both naloxone and picrotoxin were absent in bilaterally vagotomized rats. Naloxone pretreatment (25 mg/kg, i.v.) was also found to block the respiratory depressant effects of CDP in anesthetized cats, but had no effect on the cardiovascular actions of CDP. It is possible that the respiratory effects of CDP are due to its actions on GABA receptors, and that peripheral GABA receptors may mediate the protective actions of picrotoxin and naloxone.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalArchives Internationales de Pharmacodynamie et de Therapie
Volume242
Issue number1
StatePublished - 1979

Fingerprint

Chlordiazepoxide
Picrotoxin
Vagotomy
Naloxone
Respiratory Insufficiency
GABA Receptors
Maximum Tolerated Dose
Cats
Intravenous Administration

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

@article{e5b442347e6540b6b8ac63fa2c702d11,
title = "Effects of picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression",
abstract = "Intravenous administration of chlordiazepoxide (CDP) caused respiratory depression in both rats and cats. The maximally tolerated dose of CDP was found to be 165 ± 15 mg/kg, i.v., in rats. Pretreatment with picrotoxin (1.5 mg/kg) or naloxone (20 mg/kg, i.v.) significantly increased the maximally tolerated dose of CDP to 330 ± 40 mg/kg, i.v., and 270 ± 35 mg/kg, i.v., respectively. The protective effects of both naloxone and picrotoxin were absent in bilaterally vagotomized rats. Naloxone pretreatment (25 mg/kg, i.v.) was also found to block the respiratory depressant effects of CDP in anesthetized cats, but had no effect on the cardiovascular actions of CDP. It is possible that the respiratory effects of CDP are due to its actions on GABA receptors, and that peripheral GABA receptors may mediate the protective actions of picrotoxin and naloxone.",
author = "M. Billingsley and A. Suria and J. Williams",
year = "1979",
language = "English (US)",
volume = "242",
pages = "95--103",
journal = "Archives Internationales de Pharmacodynamie et de Therapie",
issn = "0003-9780",
publisher = "Wiley-Blackwell",
number = "1",

}

Effects of picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression. / Billingsley, M.; Suria, A.; Williams, J.

In: Archives Internationales de Pharmacodynamie et de Therapie, Vol. 242, No. 1, 1979, p. 95-103.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression

AU - Billingsley, M.

AU - Suria, A.

AU - Williams, J.

PY - 1979

Y1 - 1979

N2 - Intravenous administration of chlordiazepoxide (CDP) caused respiratory depression in both rats and cats. The maximally tolerated dose of CDP was found to be 165 ± 15 mg/kg, i.v., in rats. Pretreatment with picrotoxin (1.5 mg/kg) or naloxone (20 mg/kg, i.v.) significantly increased the maximally tolerated dose of CDP to 330 ± 40 mg/kg, i.v., and 270 ± 35 mg/kg, i.v., respectively. The protective effects of both naloxone and picrotoxin were absent in bilaterally vagotomized rats. Naloxone pretreatment (25 mg/kg, i.v.) was also found to block the respiratory depressant effects of CDP in anesthetized cats, but had no effect on the cardiovascular actions of CDP. It is possible that the respiratory effects of CDP are due to its actions on GABA receptors, and that peripheral GABA receptors may mediate the protective actions of picrotoxin and naloxone.

AB - Intravenous administration of chlordiazepoxide (CDP) caused respiratory depression in both rats and cats. The maximally tolerated dose of CDP was found to be 165 ± 15 mg/kg, i.v., in rats. Pretreatment with picrotoxin (1.5 mg/kg) or naloxone (20 mg/kg, i.v.) significantly increased the maximally tolerated dose of CDP to 330 ± 40 mg/kg, i.v., and 270 ± 35 mg/kg, i.v., respectively. The protective effects of both naloxone and picrotoxin were absent in bilaterally vagotomized rats. Naloxone pretreatment (25 mg/kg, i.v.) was also found to block the respiratory depressant effects of CDP in anesthetized cats, but had no effect on the cardiovascular actions of CDP. It is possible that the respiratory effects of CDP are due to its actions on GABA receptors, and that peripheral GABA receptors may mediate the protective actions of picrotoxin and naloxone.

UR - http://www.scopus.com/inward/record.url?scp=0018561248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018561248&partnerID=8YFLogxK

M3 - Article

VL - 242

SP - 95

EP - 103

JO - Archives Internationales de Pharmacodynamie et de Therapie

JF - Archives Internationales de Pharmacodynamie et de Therapie

SN - 0003-9780

IS - 1

ER -