Direct effects of morphine but not of fentanyl‐type opioids on human 5‐HT_3A receptors in outside‐out patch‐clamp studies

Abstract

Morphine is an opioid compound exhibiting special antagonistic interaction with 5-HT3A receptors. This interaction is not shared by the newer synthetic derivatives of the fentanyl-type opioids in the clinical relevant concentration range.

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

“…Synthetic opioids might interact also with other receptors, especially with the serotoninergic ones or with monoamine transporters such as norepinephrine transporter (NET) and serotonin transporter (SERT) [ 7 ], as seen for AH-7921, the effects of which were prolonged by the co-injection of serotonin (5HT) and attenuated by norepinephrine [ 31 ]. Contrarily to morphine, which has antagonistic interactions with 5HT 3A receptors [ 32 ], interaction of fentanyl with 5HT 1A and 2A receptors might lead to additional toxicity due to serotonin syndrome, especially in combination with other drugs active on the serotonin system [ 33 ]. This might explain why rescue therapy with naloxone (receptor antagonist) are noneffective, or less effective than what expected [ 34 , 35 , 36 ].…”