Inhibition of bronchial hyperresponsiveness by the GABA-agonist baclofen

Peter Vytautas Dicpinigaitis, A. M. Spungen, W. A. Bauman, A. Absgarten, P. L. Almenoff

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

γ-Aminobutyric acid (GABA) is a well-known inhibitory transmitter of the central nervous system. Recently, the presence of GABA and its receptors has been confirmed in peripheral tissues, including lung tissue. γ-Aminobutyric acid and the GABA-agonist baclofen have been shown in animal studies to inhibit airway responsiveness to various bronchoconstricting agents. The results of these investigations suggest the possibility of a role for baclofen in the therapy of human airway hyperreactivity. We recently showed that subjects with cervical spinal cord injury (quadriplegia) uniformly exhibit hyperresponsiveness to methacholine. The interruption of sympathetic airway innervation and resultant unopposed cholinergic tone occurring after transection of the cervical spine are thought to explain this phenomenon. We compared bronchial responsiveness with methacholine (PC20) in a control group of otherwise healthy quadriplegic nonsmokers (n=8) with a similar group of subjects (n=6) maintained on baclofen for the relief of muscle spasm. Mean PC20 (mg/ml) among the control group was 1.42±1.6(SD) vs 15.0±9.1 in the baclofen group (p=0.001). The inhibition of bronchial hyperresponsiveness in subjects with cervical spinal cord injury maintained on chronic baclofen therapy suggests the drug's ability to block neuronal acetylcholine release within airways, as well as a possible direct effect on airway smooth muscle. This action of baclofen, along with its documented ability in animal lung to inhibit release of other inflammatory mediators, supports further investigation of this drug as a potential therapeutic agent for asthma treatment.

Original languageEnglish (US)
Pages (from-to)758-761
Number of pages4
JournalChest
Volume106
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

GABA Agonists
Baclofen
Aminobutyrates
Methacholine Chloride
Spinal Cord Injuries
Lung
Control Groups
Quadriplegia
GABA Receptors
Spasm
gamma-Aminobutyric Acid
Cholinergic Agents
Acetylcholine
Smooth Muscle
Spine
Therapeutics
Asthma
Central Nervous System
Drug Therapy
Pharmaceutical Preparations

Keywords

  • airway innervation
  • baclofen
  • bronchial responsiveness
  • bronchoprovocation
  • GABA
  • methacholine
  • spinal cord injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Dicpinigaitis, P. V., Spungen, A. M., Bauman, W. A., Absgarten, A., & Almenoff, P. L. (1994). Inhibition of bronchial hyperresponsiveness by the GABA-agonist baclofen. Chest, 106(3), 758-761.

Inhibition of bronchial hyperresponsiveness by the GABA-agonist baclofen. / Dicpinigaitis, Peter Vytautas; Spungen, A. M.; Bauman, W. A.; Absgarten, A.; Almenoff, P. L.

In: Chest, Vol. 106, No. 3, 1994, p. 758-761.

Research output: Contribution to journalArticle

Dicpinigaitis, PV, Spungen, AM, Bauman, WA, Absgarten, A & Almenoff, PL 1994, 'Inhibition of bronchial hyperresponsiveness by the GABA-agonist baclofen', Chest, vol. 106, no. 3, pp. 758-761.
Dicpinigaitis PV, Spungen AM, Bauman WA, Absgarten A, Almenoff PL. Inhibition of bronchial hyperresponsiveness by the GABA-agonist baclofen. Chest. 1994;106(3):758-761.
Dicpinigaitis, Peter Vytautas ; Spungen, A. M. ; Bauman, W. A. ; Absgarten, A. ; Almenoff, P. L. / Inhibition of bronchial hyperresponsiveness by the GABA-agonist baclofen. In: Chest. 1994 ; Vol. 106, No. 3. pp. 758-761.
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