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CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model.
J Pain. 2006 Aug; 7(8):565-74.JP

Abstract

CHF3381 is a new low-affinity, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and reversible monoamine oxidase-A (MAO-A) inhibitor. The analgesic activity of CHF3381 was investigated in the heat-capsaicin human pain model and compared with those of gabapentin. Twenty-seven young, healthy male volunteers received a single oral dose of CHF3381 (500 mg), gabapentin (1,200 mg), or placebo in a randomized, double-blind, crossover study design. Measurements were done before and 135 to 145 minutes after treatment administration and included area of secondary hyperalgesia around the sensitized skin of the forearm (45 degrees C for 5 minutes followed by topical capsaicin for 30 minutes), area of secondary hyperalgesia after thermal sensitization of the thigh (45 degrees C for 3 minutes), heat pain detection thresholds (degrees C), and pain on a visual analogue scale after long thermal stimulation (45 degrees C for 1 minute). Compared with placebo, both gabapentin and CHF3381 significantly reduced the area of secondary hyperalgesia on the dominant forearm. Median (and interquartile range) percent values over baseline were 86% after placebo (69% to 100%), 56% (41% to 76%) after gabapentin (P < .001), and 67% (49% to 88%) after CHF3381 (P < .009). Both drugs also significantly decreased the area of secondary hyperalgesia on the dominant thigh. The other pain variables were not significantly affected. Adverse events, mainly fatigue and dizziness, were mild to moderate.

PERSPECTIVE

This article presents the antihyperalgesic effect of CHF3381, a new NMDA receptor antagonist and reversible MAO-A inhibitor, in a human pain model and might guide the proper selection of CHF3381 doses to be used in Phase 2 studies in patients with neuropathic pain.

Authors+Show Affiliations

Department of Anesthesiology, Copenhagen University Hospital, Glostrup, Denmark. olem@glostruphosp.kbhamt.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16885013

Citation

Mathiesen, Ole, et al. "CHF3381, a N-methyl-D-aspartate Receptor Antagonist and Monoamine oxidase-A Inhibitor, Attenuates Secondary Hyperalgesia in a Human Pain Model." The Journal of Pain : Official Journal of the American Pain Society, vol. 7, no. 8, 2006, pp. 565-74.
Mathiesen O, Imbimbo BP, Hilsted KL, et al. CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model. J Pain. 2006;7(8):565-74.
Mathiesen, O., Imbimbo, B. P., Hilsted, K. L., Fabbri, L., & Dahl, J. B. (2006). CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model. The Journal of Pain : Official Journal of the American Pain Society, 7(8), 565-74.
Mathiesen O, et al. CHF3381, a N-methyl-D-aspartate Receptor Antagonist and Monoamine oxidase-A Inhibitor, Attenuates Secondary Hyperalgesia in a Human Pain Model. J Pain. 2006;7(8):565-74. PubMed PMID: 16885013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CHF3381, a N-methyl-D-aspartate receptor antagonist and monoamine oxidase-A inhibitor, attenuates secondary hyperalgesia in a human pain model. AU - Mathiesen,Ole, AU - Imbimbo,Bruno P, AU - Hilsted,Karen Lisa, AU - Fabbri,Laura, AU - Dahl,Jorgen B, PY - 2005/12/09/received PY - 2006/02/03/revised PY - 2006/02/11/accepted PY - 2006/8/4/pubmed PY - 2006/10/3/medline PY - 2006/8/4/entrez SP - 565 EP - 74 JF - The journal of pain : official journal of the American Pain Society JO - J Pain VL - 7 IS - 8 N2 - UNLABELLED: CHF3381 is a new low-affinity, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and reversible monoamine oxidase-A (MAO-A) inhibitor. The analgesic activity of CHF3381 was investigated in the heat-capsaicin human pain model and compared with those of gabapentin. Twenty-seven young, healthy male volunteers received a single oral dose of CHF3381 (500 mg), gabapentin (1,200 mg), or placebo in a randomized, double-blind, crossover study design. Measurements were done before and 135 to 145 minutes after treatment administration and included area of secondary hyperalgesia around the sensitized skin of the forearm (45 degrees C for 5 minutes followed by topical capsaicin for 30 minutes), area of secondary hyperalgesia after thermal sensitization of the thigh (45 degrees C for 3 minutes), heat pain detection thresholds (degrees C), and pain on a visual analogue scale after long thermal stimulation (45 degrees C for 1 minute). Compared with placebo, both gabapentin and CHF3381 significantly reduced the area of secondary hyperalgesia on the dominant forearm. Median (and interquartile range) percent values over baseline were 86% after placebo (69% to 100%), 56% (41% to 76%) after gabapentin (P < .001), and 67% (49% to 88%) after CHF3381 (P < .009). Both drugs also significantly decreased the area of secondary hyperalgesia on the dominant thigh. The other pain variables were not significantly affected. Adverse events, mainly fatigue and dizziness, were mild to moderate. PERSPECTIVE: This article presents the antihyperalgesic effect of CHF3381, a new NMDA receptor antagonist and reversible MAO-A inhibitor, in a human pain model and might guide the proper selection of CHF3381 doses to be used in Phase 2 studies in patients with neuropathic pain. SN - 1526-5900 UR - https://www.unboundmedicine.com/medline/citation/16885013/CHF3381_a_N_methyl_D_aspartate_receptor_antagonist_and_monoamine_oxidase_A_inhibitor_attenuates_secondary_hyperalgesia_in_a_human_pain_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-5900(06)00544-X DB - PRIME DP - Unbound Medicine ER -