title: Neamine and 2-deoxystreptamine neomycin derivatives exhibit antinociceptive activity in rat models of phasic, incision and neuropathic pain.
abstract: OBJECTIVE
  To assess the antinociceptive activity of the neomycin derivatives neamine and 2-deoxystreptamine following intraspinal administration in rats.
  
  
  METHODS
  We used the tail-flick test and measured the threshold to mechanical stimulation in models of incisional and neuropathic pain.
  
  
  RESULTS
  The derivatives produced antinociception in the tail-flick test and reduced mechanical allodynia in models of incisional and neuropathic pain. The approximate ED50 in milligrams (confidence limits in parenthesis) in these tests were 1.35 mg (0.61; 2.95), 0.20 mg (0.14; 0.27) and 0.28 mg (0.12; 0.63) for neamine, and 1.05 mg (0.68; 1.60), 0.78 mg (0.776; 0.783) and 0.79 mg (0.46; 1.34) for 2-deoxystreptamine, respectively. Neamine was more potent than 2-deoxystreptamine in the incisional and neuropathic pain models, but they had similar potency in the tail-flick test. Tetra-azidoneamine, a neamine derivative in which free amino groups are replaced with azido groups, did not change the incisional mechanical allodynia. The reduction of incisional allodynia by neamine and 2-deoxystreptamine was transitorily antagonized by intrathecal administration of calcium chloride.
  
  
  CONCLUSIONS
  The intraspinal administration of neamine and 2-deoxystreptamine is antinociceptive in rats. The presence of amino groups in the structure of these derivatives is fundamental to their antinociceptive effect, which may be due to a calcium antagonist activity.
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Wiliam A
authors.initials: WA
authors.lastname: Prado
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Rossaneis
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Luis Otávio B
authors.initials: LO
authors.lastname: Zamoner
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Corrado
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005601:Framycetin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006595:Hexosamines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D015394:Molecular Structure; D009437:Neuralgia / Q000503:physiopathology / Q000517:prevention & control*; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010149:Postoperative Pain / Q000503:physiopathology / Q000517:prevention & control*; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000700:Analgesics; D006595:Hexosamines; D005601:Framycetin; C488396:neamine; C007265:2-deoxystreptamine
keywords: 2-deoxystreptamine; aminoglycoside antibiotic; incision pain; neamine; neuropathic pain