title: Discovery of tetrahydropyrido[4,3-d]pyrimidine derivatives for the treatment of neuropathic pain.
abstract: A series of tetrahydropyridopyrimidine derivatives were synthesized and evaluated for neurotoxicity and peripheral analgesic activity followed by assessment of antiallodynic and antihyperalgesic potential in two peripheral neuropathic pain models, the chronic constriction injury (CCI) and partial sciatic nerve ligation (PSNL). Compounds (4b and 4d) exhibiting promising efficacies in four behavioral assays of allodynia and hyperalgesia (spontaneous pain, tactile allodynia, cold allodynia and mechanical hyperalgesia) were quantified for their ED50 values (15.12-65.10mg/kg). Studies carried out to assess the underlying mechanism revealed that the compounds suppressed the inflammatory component of the neuropathic pain and prevented oxidative and nitrosative stress.
authors.affiliation: Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District-500078, Andhra Pradesh, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District-500078, Andhra Pradesh, India.
authors.forename: Vanamala
authors.initials: V
authors.lastname: Deekshith
authors.affiliation: Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District-500078, Andhra Pradesh, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Semwal
authors.affiliation: Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District-500078, Andhra Pradesh, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District-500078, Andhra Pradesh, India. Electronic address: pyogee@hyderabad.bits-pilani.ac.in.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D055808:Drug Discovery; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy*; D011743:Pyrimidines / Q000737:chemistry*; D012584:Sciatic Nerve / Q000601:surgery
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011743:Pyrimidines; C030986:pyrimidine
keywords: Antiallodynic; Antihyperalgesic; Neuropathic pain; Nitric oxide; Tetrahydropyridopyrimidine