Abstract：
AIMS:Ventilatory disturbance is a fatal side-effect of opioid analgesics. Separation of analgesia from ventilatory depression is important for therapeutic use of opioids. It has been suggested that opioid-induced ventilatory depression results from a decrease in adenosine 3',5'-cyclic monophosphate content in the respiratory-related neurons. Therefore, we examined the effects of caffeine, a methylxanthine non-selective phosphodiesterase (PDE) inhibitor with adenosine antagonistic activity, and rolipram, a racetam selective PDE4 inhibitor, on ventilatory depression induced by morphine. MAIN METHODS:Spontaneous ventilation and paw withdrawal responses to nociceptive thermal stimulation were measured in anesthetized rats simultaneously. The efferent discharge of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed and artificially ventilated rats. KEY FINDINGS:Rolipram (0.1 and 0.3 mg/kg, i.v.) and caffeine (3.0 and 10.0 mg/kg, i.v.) relieved morphine (1.0 mg/kg, i.v.)-induced ventilatory depression but had no discernible effect on its analgesic action. Rolipram (0.3 and 1.0 mg/kg, i.v.) and caffeine (10.0 and 20.0 mg/kg, i.v.) recovered morphine (3.0 mg/kg, i.v.)-induced prolongation and flattening of inspiratory discharge in the phrenic nerve. SIGNIFICANCE:Inhibition of PDE4 may be a possible approach for overcoming morphine-induced ventilatory depression without loss of analgesia.
journal_name
Life Scijournal_title
Life sciencesauthors
Kimura S,Ohi Y,Haji Adoi
10.1016/j.lfs.2015.02.006subject
Has Abstractpub_date
2015-04-15 00:00:00pages
32-8eissn
0024-3205issn
1879-0631pii
S0024-3205(15)00099-5journal_volume
127pub_type
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