Occupancy of serotonin transporter by tramadol: a positron emission tomography study with [11C]DASB.

Abstract

Tramadol is used for the treatment of pain, and it is generally believed to activate the μ-opioid receptor and inhibit serotonin (5-HT) and norepinephrine (NE) transporters. Recent findings from animal experiments suggest that 5-HT reuptake inhibition in brain is related to pain reduction. However, there has been no report of 5-HT transporter (5-HTT) occupancy by tramadol at clinical doses in humans. In the present study, we investigated 5-HTT occupancy by tramadol in five subjects receiving various doses of tramadol by using positron emission tomography (PET) scanning with the radioligand [11C]DASB. Our data showed that mean 5-HTT occupancies in the thalamus by single doses of tramadol were 34.7% at 50 mg and 50.2% at 100 mg. The estimated median effective dose (ED50) of tramadol was 98.1 mg, and the plasma concentration was 0.33 μg/ml 2 h after its administration; 5-HTT occupancy by tramadol was dose-dependent. We estimated 5-HTT occupancy at 78.7% upon taking an upper limit dose (400 mg) of tramadol. The results of the present study support the finding that 5-HTT inhibition is involved in the mechanism underlying the analgesic effect of tramadol in humans, and a clinical dose of tramadol sufficiently inhibits 5-HTT reuptake; this inhibition is similar to that shown by selective serotonin reuptake inhibitors (SSRIs).

• Authors: Kohei Ogawa, Amane Tateno, Ryosuke Arakawa, Takeshi Sakayori, Yumiko Ikeda, Hidenori Suzuki, Yoshiro Okubo
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 17 Issue 6 Pg. 845-50 (Jun 2014) ISSN: 1469-5111 [Electronic] England
• PMID: 24423243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Benzylamines
• Carbon Radioisotopes
• N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine
• Radiopharmaceuticals
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Tramadol

Topics

• Adult
• Analgesics, Opioid (blood, pharmacology)
• Benzylamines
• Brain (diagnostic imaging, drug effects, metabolism)
• Carbon Radioisotopes
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Positron-Emission Tomography
• Radiopharmaceuticals
• Serotonin Plasma Membrane Transport Proteins (metabolism)
• Thalamus (diagnostic imaging, drug effects, metabolism)
• Tramadol (blood, metabolism, pharmacology)
• Young Adult