An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UV(B)-inflamed and normal skin

Br J Clin Pharmacol. 75:2 / 404–414 2012 Jul 10.2012
DOI: 10.1111/j.1365-2125.2012.04377.x.


AIMS: Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG Peak-to-Peak (PtP) amplitude were used to determine acute antinociceptive/ antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared to active controls and placebo in normal and UV(B)-inflamed skin of healthy humans.
METHODS: This was a randomized, placebo- and active-controlled, double-blind, intra-individual-crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg, and placebo. Painful stimuli were induced by CO(2)-laser on normal and UV(B)-inflamed skin. LEPs and visual analog scale (VAS-Pain) ratings were taken at baseline and hourly up to 8 hours post-dose from both skin types.
RESULTS: Compared to placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UV(B)-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8-hour period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8-hour period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared to placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4, and 9.4 ng/mL for the 0.5, 2, and 6 mg doses, respectively. There were no clinically significant safety findings.
CONCLUSIONS: TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation.

Link to full paper here.

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About Klaus Schaffler

Dr. med. Klaus Schaffler (MD) has been specializing in the electrophysiology and pharmacology of the human central nervous system (CNS) – as well as in the field of human experimental pain research. During this development process, HPR Dr. Schaffler GmbH has issued over 175 presentations/ publications (sharing more than 50 on pain/ analgesia) and has conducted more than 150 phase-I studies with quite different objectives.