Respiratory effects of baclofen and 3‐aminopropylphosphinic acid in guinea‐pigs

Abstract

1 The effects of the GABAB receptor agonists, baclofen and 3-aminopropylphosphinic acid given by the subcutaneous or intracerebroventricular (i.c.v.) route were examined on minute ventilation (V), tidal volume (VT) and respiratory rate (f) due to room air and carbon dioxide (CO2)-enriched gas hyperventilation in conscious guinea-pigs.2 Baclofen (0.3-10 mg kg-', s.c.) produced a dose-dependent inhibition of V and f due to room air and CO2 inhalation. The maximum inhibition of room air breathing V was 85% ± 3 and f was 74% 3 at 10 mg kg-1, s.c. The maximum effects on C02-induced hyperventilation were 68% ± 9 and 51% 6, for V and f respectively. Only the highest dose of baclofen studied (10 mg kg-') produced a significant inhibition of VT due to room air breathing (46% ± 6) and CO2 breathing (38% ± 11). 3 3-APPi (0. 7 These results show that baclofen inhibits ventilation due to room air breathing, and attenuates the hyperventilation response to CO2 inhalation. The peripherally acting GABAB agonist, 3-APPi had no effect on ventilation. These findings demonstrate that the respiratory depressant effects of baclofen are due to activation of CNS GABAB receptors and indicates that only GABAB receptor agonists that penetrate into the CNS may cause respiratory depression.

Postnatal development of GABAB receptor‐mediated modulation of voltage‐activated Ca2+ currents in mouse brain‐stem neurons

“…1993 ; Champagnat & Richter 1994), rat ( Brockhaus & Ballanyi 1998; Hayashi & Lipski 1992; Johnson et al . 1996 ), guinea pig ( Hey et al . 1995 ) and rabbit ( Schmid et al .…”

The mechanisms of sudden-onset type adverse reactions to oseltamivir

“…Baclofen, a GABA B agonist induces respiratory arrest (apnea) in high dose in both animals [77] and in human [78]. …”

Central Mechanisms II: Pharmacology of Brainstem Pathways

“…The concept of receptor specificity is relevant not only to the receptor subtype actuated by a given drug, but also to the physiological system that is affected. For example, both morphine (a specific μ-opioid receptor agonist) and baclofen (a specific GABA-B receptor agonist) are known to be respiratory depressant agents (Adcock et al 1988; Hey et al 1995). However, in the guinea pig the doses of these drugs necessary for respiratory depression are greater than those required for inhibition of cough (Adcock et al 1988; Bolser et al 1994; Hey et al 1995).…”

“…For example, both morphine (a specific μ-opioid receptor agonist) and baclofen (a specific GABA-B receptor agonist) are known to be respiratory depressant agents (Adcock et al 1988; Hey et al 1995). However, in the guinea pig the doses of these drugs necessary for respiratory depression are greater than those required for inhibition of cough (Adcock et al 1988; Bolser et al 1994; Hey et al 1995). Presumably, each drug acts specifically at its respective receptor subtype to inhibit both cough and breathing, but the potency of the drugs to inhibit these behaviors is different.…”