Send to

Choose Destination
Am J Physiol Regul Integr Comp Physiol. 2006 Feb;290(2):R405-13. Epub 2005 Sep 15.

Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats.

Author information

Brain Function Research Unit, School of Physiology, University of the Witwatersrand, South Africa.


Neurophysiological studies have shown that serotonergic ligands that bind to 5-HT1A, 5-HT7, and 5-HT4 serotonin receptors in brain stem have beneficial effects on respiratory neurons during opioid-induced respiratory depression. The effect of these ligands on respiratory function and pulmonary performance has not been studied. We therefore examined the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist of 5-HT1A and 5-HT7 receptors, and zacopride, an agonist of 5-HT4 receptors, to establish whether these ligands would reverse opioid-induced respiratory depression and hypoxia without affecting the immobilizing properties of the opioid drug etorphine. When etorphine was used to sedate and immobilize goats, it significantly decreased respiratory rate (P = 0.013), percent hemoglobin oxygen saturation (P < 0.0001), and arterial oxygen partial pressure [Pa(O2); F(10,70) = 5.67, P < 0.05] and increased arterial carbon dioxide partial pressure [F(10,70) = 3.87, P < 0.05] and alveolar-arterial oxygen partial pressure gradient [A-a gradients; F(10,70) = 8.23, P < 0.0001]. Zacopride and 8-OH-DPAT, coadministered with etorphine, both attenuated the effects of etorphine; respiration rates did not decrease, and percent hemoglobin oxygen saturation and Pa(O2) remained elevated. Zacopride decreased the hypercapnia, indicating an improvement in ventilation, whereas 8-OH-DPAT did not affect the hypercapnia and, therefore, did not improve ventilation. The main beneficial effect of 8-OH-DPAT was on the pulmonary circulation; it improved oxygen diffusion, indicated by the normal A-a gradients, presumably by improving ventilation perfusion ratios. Neither zacopride nor 8-OH-DPAT reversed etorphine-induced catatonic immobilization. We conclude that serotonergic drugs that act on 5-HT1A, 5-HT7, and 5-HT4 receptors reverse opioid-induced respiratory depression and hypoxia without reversing catatonic immobilization.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center