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ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid], a novel histamine H1 receptor antagonist, produces potent and selective antinociceptive effects on dorsal horn neurons after inflammation and neuropathy.
J Pharmacol Exp Ther. 2004 Jun; 309(3):1230-8.JP

Abstract

We characterized the effect of a novel selective histamine H1 receptor antagonist, (R)-1-(3-(10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid (ReN-1869), on the responses of dorsal horn neurons in anesthetized rats after carrageenan induced-inflammation and peripheral neuropathy (L5/6 spinal nerve ligation; SNL). ReN-1869 was administered systemically (0.1-4 mg/kg), and drug effects were assessed using a wide range of peripheral electrical and natural stimuli (brush, von Frey filaments, and heat). Comparisons were made between unoperated naive groups and either carrageenan inflamed or SNL rats. ReN-1869 produced little effect on the electrically evoked responses (wind-up, Abeta-, Adelta-, and C-fiber-evoked responses); however, it significantly attenuated neuronal responses to noxious heat in carrageenan and SNL rats. A robust effect was seen with the low-threshold mechanical punctate (von Frey 9 g) stimuli, which were selectively inhibited by ReN-1869 after tissue and nerve injury. These inhibitory actions were in marked contrast to the naive animal group, where only nonsignificant effects were observed. To investigate whether the actions of ReN-1869 are mediated via the antagonism of histamine H1 receptors, the effects of this novel compound were compared with that of another H1 receptor antagonist, mepyramine (1-20 mg/kg). Systemic mepyramine produced strong inhibitions of the 9-g von Frey-evoked responses in carrageenan and SNL rats. The similar pharmacological profile of these two compounds suggests for a similar mechanism of action. We propose that ReN-1869 may represent a novel agent for the treatment of certain modalities of persistent pain states, in particular for the treatment of mechanical allodynia.

Authors+Show Affiliations

Department of Pharmacology, University College London, WC1E 6BT London, UK. ucklrsu@ucl.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14988422

Citation

Suzuki, R, et al. "ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine Carboxylic Acid], a Novel Histamine H1 Receptor Antagonist, Produces Potent and Selective Antinociceptive Effects On Dorsal Horn Neurons After Inflammation and Neuropathy." The Journal of Pharmacology and Experimental Therapeutics, vol. 309, no. 3, 2004, pp. 1230-8.
Suzuki R, Edwards M, Dickenson AH. ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid], a novel histamine H1 receptor antagonist, produces potent and selective antinociceptive effects on dorsal horn neurons after inflammation and neuropathy. J Pharmacol Exp Ther. 2004;309(3):1230-8.
Suzuki, R., Edwards, M., & Dickenson, A. H. (2004). ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid], a novel histamine H1 receptor antagonist, produces potent and selective antinociceptive effects on dorsal horn neurons after inflammation and neuropathy. The Journal of Pharmacology and Experimental Therapeutics, 309(3), 1230-8.
Suzuki R, Edwards M, Dickenson AH. ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine Carboxylic Acid], a Novel Histamine H1 Receptor Antagonist, Produces Potent and Selective Antinociceptive Effects On Dorsal Horn Neurons After Inflammation and Neuropathy. J Pharmacol Exp Ther. 2004;309(3):1230-8. PubMed PMID: 14988422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ReN-1869 [(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid], a novel histamine H1 receptor antagonist, produces potent and selective antinociceptive effects on dorsal horn neurons after inflammation and neuropathy. AU - Suzuki,R, AU - Edwards,M, AU - Dickenson,A H, Y1 - 2004/02/26/ PY - 2004/2/28/pubmed PY - 2004/7/2/medline PY - 2004/2/28/entrez SP - 1230 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 309 IS - 3 N2 - We characterized the effect of a novel selective histamine H1 receptor antagonist, (R)-1-(3-(10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid (ReN-1869), on the responses of dorsal horn neurons in anesthetized rats after carrageenan induced-inflammation and peripheral neuropathy (L5/6 spinal nerve ligation; SNL). ReN-1869 was administered systemically (0.1-4 mg/kg), and drug effects were assessed using a wide range of peripheral electrical and natural stimuli (brush, von Frey filaments, and heat). Comparisons were made between unoperated naive groups and either carrageenan inflamed or SNL rats. ReN-1869 produced little effect on the electrically evoked responses (wind-up, Abeta-, Adelta-, and C-fiber-evoked responses); however, it significantly attenuated neuronal responses to noxious heat in carrageenan and SNL rats. A robust effect was seen with the low-threshold mechanical punctate (von Frey 9 g) stimuli, which were selectively inhibited by ReN-1869 after tissue and nerve injury. These inhibitory actions were in marked contrast to the naive animal group, where only nonsignificant effects were observed. To investigate whether the actions of ReN-1869 are mediated via the antagonism of histamine H1 receptors, the effects of this novel compound were compared with that of another H1 receptor antagonist, mepyramine (1-20 mg/kg). Systemic mepyramine produced strong inhibitions of the 9-g von Frey-evoked responses in carrageenan and SNL rats. The similar pharmacological profile of these two compounds suggests for a similar mechanism of action. We propose that ReN-1869 may represent a novel agent for the treatment of certain modalities of persistent pain states, in particular for the treatment of mechanical allodynia. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/14988422/ReN_1869_[_R__1__3__1011_dihydro_5H_dibenzo[ad]cyclohepten_5_ylidene__1_propyl__3_piperidine_carboxylic_acid]_a_novel_histamine_H1_receptor_antagonist_produces_potent_and_selective_antinociceptive_effects_on_dorsal_horn_neurons_after_inflammation_and_neuropathy_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14988422 DB - PRIME DP - Unbound Medicine ER -