title: DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain.
abstract: DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve ligation and chronic constriction injury) and inflammatory (Complete Freund's Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent than pregabalin and indomethacin. Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities.
authors.affiliation: Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63121, USA.
authors.forename: Parthasarathi
authors.initials: P
authors.lastname: Rajagopalan
authors.affiliation: SB Drug Discovery, Ltd, Todd Campus, West of Scotland Science Park, Glasgow, Scotland G20 0XA, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Tracey
authors.affiliation: Department of Pharmacological and Physiological Sciences, St. Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
authors.forename: Zhoumou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63121, USA.
authors.forename: Acintya
authors.initials: A
authors.lastname: Bandyopadhyaya
authors.affiliation: Incozen Therapeutics, Ltd, 450 Alexandria Knowledge Park, Hyderabad 500078, Andhra Pradesh, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Veeraraghavan
authors.affiliation: Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63121, USA.
authors.forename: Desikan R
authors.initials: DR
authors.lastname: Rajagopalan
authors.affiliation: Department of Pharmacological and Physiological Sciences, St. Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Salvemini
authors.affiliation: SB Drug Discovery, Ltd, Todd Campus, West of Scotland Science Park, Glasgow, Scotland G20 0XA, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: McPhee
authors.affiliation: Incozen Therapeutics, Ltd, 450 Alexandria Knowledge Park, Hyderabad 500078, Andhra Pradesh, India.
authors.forename: Srikant
authors.initials: S
authors.lastname: Viswanadha
authors.affiliation: Daya Drug Discoveries, Inc., University of Missouri, St. Louis, One University Blvd., St. Louis, MO 63121, USA. Electronic address: raghavanr@daya-dd.com.
authors.forename: Raghavan
authors.initials: R
authors.lastname: Rajagopalan
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001381:Azepines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement; D051381:Rats; D013127:Spinal Nerves / Q000187:drug effects* / Q000473:pathology
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D002243:Carbolines; C000595509:DDD-028
keywords: CCI model; Inflammatory pain; Neuropathic pain; Pyridoinolobenzazepine; SNL model