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.

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.
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