Dual action of morphine on fetal breathing movements.
Morphine has been reported to both stimulate and suppress fetal breathing movements (FBM). In light of these conflicting reports, we have conducted a systematic dose-response analysis of the effects of morphine on FBM in 27 fetal lambs. Morphine was infused directly to the fetus in doses ranging from 0.075 to 80 mg/hr. Low doses (0.075-2.5 mg/hr) resulted in a progressive increase in the relative incidence of FBM, whereas higher doses (greater than 2.5 mg/hr) decreased FBM with total apnea observed at 80 mg/hr. This biphasic response can be fitted as the sum of two sigmoidal log dose-response curves. Both stimulation and suppression of FBM by morphine were abolished by naloxone pretreatment, indicating that both responses are mediated by activation of opioid receptors. The dual action of morphine on FBM may be due to different opioid receptor subtypes or different sites of action.
Szeto
H H
HH
Department of Pharmacology, Cornell University Medical College, New York, New York.
Zhu
Y S
YS
Umans
J G
JG
Dwyer
G
G
Clare
S
S
Amione
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*; D012756:Sheep
D009270:Naloxone; D009020:Morphine