PMID- 7773531
OWN - NLM
STAT- MEDLINE
DCOM- 19950711
LR  - 20190512
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 114
IP  - 4
DP  - 1995 Feb
TI  - Respiratory effects of baclofen and 3-aminopropylphosphinic acid in guinea-pigs.
PG  - 735-8
AB  - 1. The effects of the GABAB receptor agonists, baclofen and 
      3-aminopropylphosphinic acid (3-APPi) 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-1, 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 CO2-induced 
      hyperventilation were 68% +/- 9 and 51% +/- 6, for V and f respectively. Only the 
      highest dose of baclofen studied (10 mg kg-1) produced a significant inhibition 
      of VT due to room air breathing (46% +/- 6) and CO2 breathing (38% +/- 11). 3. 
      3-APPi (0.3-100 mg kg-1, s.c.) did not affect V, VT or f due to room air 
      breathing or CO2 inhalation at any dose tested. Also, i.c.v. administration of 
      3-APPi (100 micrograms) did not affect ventilatory responses due to room air 
      breathing or CO2 inhalation. 4. Pretreatment with the GABAB antagonist, CGP 35348 
      3-aminopropyl-(diethoxymethyl) phosphinic acid (3-30 mg kg-1, s.c.) blocked the 
      respiratory depressant effects of baclofen (3 mg kg-1, s.c.) in a dose-related 
      fashion. 5. Intracerebroventricular (i.c.v.) administration of CGP 35348 (50 
      micrograms) blocked the respiratory depressant effects of baclofen. CGP 35348 
      given alone either i.c.v. or s.c. had no effects on respiration due to room air 
      or CO2 inhalation.6. Pretreatment with either the GABAA antagonist bicuculline 
      (30 mg kg-1, s.c.) or the opioid antagonist, naloxone (1 mg kg-1, s.c.) had no 
      effect on the respiratory depressant action of baclofen(3 mg kg-1, s.c.).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.
FAU - Hey, J A
AU  - Hey JA
AD  - Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
FAU - Mingo, G
AU  - Mingo G
FAU - Bolser, D C
AU  - Bolser DC
FAU - Kreutner, W
AU  - Kreutner W
FAU - Krobatsch, D
AU  - Krobatsch D
FAU - Chapman, R W
AU  - Chapman RW
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (GABA Agonists)
RN  - 0 (GABA-A Receptor Antagonists)
RN  - 0 (GABA-B Receptor Antagonists)
RN  - 0 (Organophosphorus Compounds)
RN  - 103680-47-3 (3-aminopropylphosphinic acid)
RN  - 142M471B3J (Carbon Dioxide)
RN  - 36B82AMQ7N (Naloxone)
RN  - 87TI61875H (CGP 35348)
RN  - H789N3FKE8 (Baclofen)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Administration, Inhalation
MH  - Analysis of Variance
MH  - Animals
MH  - Baclofen/administration & dosage/*pharmacology
MH  - Bicuculline/administration & dosage/pharmacology
MH  - Carbon Dioxide/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - GABA Agonists/administration & dosage/*pharmacology
MH  - GABA-A Receptor Antagonists
MH  - GABA-B Receptor Antagonists
MH  - Guinea Pigs
MH  - Injections, Intraventricular
MH  - Injections, Subcutaneous
MH  - Male
MH  - Naloxone/administration & dosage/pharmacology
MH  - Organophosphorus Compounds/administration & dosage/*pharmacology
MH  - Pulmonary Ventilation/drug effects
MH  - Respiration/*drug effects
MH  - Tidal Volume/drug effects
PMC - PMC1510199
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
PMCR- 1996/02/01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
PHST- 1996/02/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1995.tb13265.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1995 Feb;114(4):735-8. doi: 10.1111/j.1476-5381.1995.tb13265.x.