5-HT4(a) receptors avert opioid-induced
breathing depression without loss of analgesia
by
Manzke T, Guenther U, Ponimaskin EG, Haller M,
Dutschmann M, Schwarzacher S, Richter DW.
Department of Neuro- and Sensory Physiology,
University of Goettingen, Humboldtallee 23,
37073 Goettingen, Germany.
Science. 2003 Jul 11;301(5630):226-9

ABSTRACT

Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor-specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.

Pain
LAAM
Codeine
Tolerance
Knockout mice
Opium timeline
Opioid receptors
The Pleasures of Opium

Refs
HOME
HedWeb
Cannabis.net
BLTC Research
Designer Drugs
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best To Take Crack Cocaine?