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Int J Neuropsychopharmacol. 2014 Jun;17(6):845-50. doi: 10.1017/S1461145713001764. Epub 2014 Jan 15.

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

Author information

1
Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
2
Department of Pharmacology, Nippon Medical School, Tokyo, Japan.

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).

PMID:
24423243
DOI:
10.1017/S1461145713001764
[Indexed for MEDLINE]
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