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Antinociceptive activity of α4β2* neuronal nicotinic receptor agonist A-366833 in experimental models of neuropathic and inflammatory pain.
Eur J Pharmacol. 2011 Oct 01; 668(1-2):155-62.EJ

Abstract

Nerve injury, diabetes and cancer therapies are often associated with painful neuropathy. The mechanism underlying neuropathic pain remains poorly understood. The current therapies have limited efficacy and are associated with dose-limiting side effects. Compounds which act at nicotinic acetylcholine receptors have also been reported to show antinociceptive activity. Among those, tebanicline (ABT-594) a potent nicotinic acetylcholine receptor agonist demonstrated analgesic effects across a broad range of preclinical models of nociceptive and neuropathic pain. Another nicotinic acetylcholine receptor agonist, 5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) from the same group produced significant antinociceptive effects in writhing pain (abdominal constriction), acute thermal pain (hot box), persistent chemical pain (formalin induced) and neuropathic pain. In the present study, we have demonstrated the efficacy of A-366833 in rat models of chronic constriction injury, partial sciatic nerve ligation, spinal nerve ligation, diabetes, chemotherapy induced neuropathic pain and complete Freund's adjuvant induced inflammatory pain. A-366833 (1, 3 and 6 mg/kg) produced significant antihyperalgesic effects in partial sciatic nerve ligation, chronic constriction injury and spinal nerve ligation models. In the diabetic and chemotherapy induced neuropathic models compound exerted antinociceptive activity and reduction in the mechanical hyperalgesia was observed. A-366833 dose dependently attenuated mechanical hyperalgesia in complete Freund's adjuvant induced inflammatory pain model. These results demonstrated broad-spectrum antinociceptive properties of A-366833 in both neuropathic and inflammatory pain models.

Authors+Show Affiliations

Department of Pharmacology, Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road No 5, Avenue-7, Banjara Hills, Hyderabad, 500034, India. nvsrk@suven.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21756895

Citation

Nirogi, Ramakrishna, et al. "Antinociceptive Activity of Α4β2* Neuronal Nicotinic Receptor Agonist A-366833 in Experimental Models of Neuropathic and Inflammatory Pain." European Journal of Pharmacology, vol. 668, no. 1-2, 2011, pp. 155-62.
Nirogi R, Jabaris SL, Jayarajan P, et al. Antinociceptive activity of α4β2* neuronal nicotinic receptor agonist A-366833 in experimental models of neuropathic and inflammatory pain. Eur J Pharmacol. 2011;668(1-2):155-62.
Nirogi, R., Jabaris, S. L., Jayarajan, P., Abraham, R., Shanmuganathan, D., Rasheed, M. A., Royapalley, P. K., & Goura, V. (2011). Antinociceptive activity of α4β2* neuronal nicotinic receptor agonist A-366833 in experimental models of neuropathic and inflammatory pain. European Journal of Pharmacology, 668(1-2), 155-62. https://doi.org/10.1016/j.ejphar.2011.06.032
Nirogi R, et al. Antinociceptive Activity of Α4β2* Neuronal Nicotinic Receptor Agonist A-366833 in Experimental Models of Neuropathic and Inflammatory Pain. Eur J Pharmacol. 2011 Oct 1;668(1-2):155-62. PubMed PMID: 21756895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antinociceptive activity of α4β2* neuronal nicotinic receptor agonist A-366833 in experimental models of neuropathic and inflammatory pain. AU - Nirogi,Ramakrishna, AU - Jabaris,Sugin Lal, AU - Jayarajan,Pradeep, AU - Abraham,Renny, AU - Shanmuganathan,Dhanalakshmi, AU - Rasheed,Mohammed Abdul, AU - Royapalley,Praveen Kumar, AU - Goura,Venkatesh, Y1 - 2011/07/03/ PY - 2011/04/11/received PY - 2011/06/02/revised PY - 2011/06/15/accepted PY - 2011/7/16/entrez PY - 2011/7/16/pubmed PY - 2011/12/28/medline SP - 155 EP - 62 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 668 IS - 1-2 N2 - Nerve injury, diabetes and cancer therapies are often associated with painful neuropathy. The mechanism underlying neuropathic pain remains poorly understood. The current therapies have limited efficacy and are associated with dose-limiting side effects. Compounds which act at nicotinic acetylcholine receptors have also been reported to show antinociceptive activity. Among those, tebanicline (ABT-594) a potent nicotinic acetylcholine receptor agonist demonstrated analgesic effects across a broad range of preclinical models of nociceptive and neuropathic pain. Another nicotinic acetylcholine receptor agonist, 5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) from the same group produced significant antinociceptive effects in writhing pain (abdominal constriction), acute thermal pain (hot box), persistent chemical pain (formalin induced) and neuropathic pain. In the present study, we have demonstrated the efficacy of A-366833 in rat models of chronic constriction injury, partial sciatic nerve ligation, spinal nerve ligation, diabetes, chemotherapy induced neuropathic pain and complete Freund's adjuvant induced inflammatory pain. A-366833 (1, 3 and 6 mg/kg) produced significant antihyperalgesic effects in partial sciatic nerve ligation, chronic constriction injury and spinal nerve ligation models. In the diabetic and chemotherapy induced neuropathic models compound exerted antinociceptive activity and reduction in the mechanical hyperalgesia was observed. A-366833 dose dependently attenuated mechanical hyperalgesia in complete Freund's adjuvant induced inflammatory pain model. These results demonstrated broad-spectrum antinociceptive properties of A-366833 in both neuropathic and inflammatory pain models. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/21756895/Antinociceptive_activity_of_α4β2__neuronal_nicotinic_receptor_agonist_A_366833_in_experimental_models_of_neuropathic_and_inflammatory_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(11)00739-4 DB - PRIME DP - Unbound Medicine ER -