TABLE 1

Inhibition of opioid binding, monoamine transporter binding, and synaptosomal monoamine uptake by tapentadol and reference compounds

Results are the means of sets of experiments performed in triplicate (n = 3) or quadruplicate (n = 4).

	K_i Values (μM ± S.E.M.)
	Rat Opioid Receptor Binding Assays					Rat Synaptosomal Monoamine Uptake Assays		Human Recombinant Monoamine Transporter Binding Assays
	[³H]Naloxone (MOR Antagonist)	[³H]pCl-DPDPE (DOR Agonist)	[³H]Cl-977 (KOR Agonist)	[³H]l-NE	[³H]5-HT	[³H]Nisoxetine (NE Transporter)	[³H]Imipramine (5-HT Transporter)
Tapentadol	0.096 ± 0.009	0.97 ± 0.01	0.91 ± 0.09	0.48 ± 0.11	2.37 ± 0.54	8.80 ± 1.17	5.28 ± 0.58
Morphine	0.0022 ± 0.0001	0.080 ± 0.001	0.17 ± 0.02	>100	>100	N.D.	N.D.
Codeine	1.3 ± 0.5	5.5 ± 0.6	14 ± 2.0	>100	>100	N.D.	N.D.
Tapentadol-Glucuronide	Inactive^a	N.D.	N.D.	>100	>100	N.D.	N.D.
Venlafaxine	N.D.	N.D.	N.D.	0.45 ± 0.03	0.062 ± 0.013	6.57 ± 1.25	0.035 ± 0.0070
Fluoxetine	N.D.	N.D.	N.D.	0.53 ± 0.176	0.026 ± 0.0018	2.91 ± 0.50	0.0015 ± 0.0001
Duloxetine	N.D.	N.D.	N.D.	0.011 ± 0.0025	0.0046 ± 0.00034	0.014 ± 0.0020	0.00035 ± 0.00005
Nisoxetine	N.D.	N.D.	N.D.	0.0017 ± 0.00015	0.37 ± 0.045	0.011 ± 0.0012	0.17 ± 0.032

N.D., not determined; pCl-DPDPE, [d-Pen²,pCl-Phe⁴,d-Pen⁵]-enkephalin; CI-977, enandoline.
↵ a Less than 10% inhibition at 10 μM (at human recombinant MOR); data for reference compounds were in part published in Frink et al. (1996).