title: Activities of 2-phthalimidethyl nitrate and 2-phthalimidethanol in the models of nociceptive response and edema induced by formaldehyde in mice and preliminary investigation of the underlying mechanisms.
abstract: The activities of 2-phthalimidethyl nitrate (PTD-NO) and 2-phthalimidethanol (PTD-OH) were recently demonstrated in models of pain and inflammation. We expanded our investigation by evaluating their activities in models of nociceptive and inflammatory pain and inflammatory edema, the preliminary pharmacokinetic parameter for PTD-NO and the role of opioid and cannabinoid pathways in the activity of analogs. Per os (p.o.) administration of PTD-NO or PTD-OH, 1h before intraplantar injection of formaldehyde, inhibited both phases of the nociceptive response (500 and 750 mg/kg) and paw edema (125, 250, 500 and 750 mg/kg). After p.o. administration of PTD-NO, peak plasma concentrations of PTD-NO and PTD-OH were found 0.92 and 1.13 h, respectively. The plasma concentrations of PTD-NO were higher than those of PTD-OH. Intraperitoneal (i.p.) administration of CB1 (AM251) or CB2 (AM630) cannabinoid receptor antagonists (4 or 8 mg/kg, -30 min) or opioid antagonist naltrexone (5 or 10mg/kg, -30 min) did not affect the antinociceptive activities of the analogs. AM251 (8 mg/kg, i.p., -30 min) attenuated the antiedematogenic activity of both analogs, while naltrexone (10mg/kg, i.p., -30 min) only attenuated the antiedematogenic activity of PTD-NO. The antiedematogenic activities of both analogs were not affected by the CB2 cannabinoid antagonist AM630 (4 or 8 mg/kg, i.p., -30 min). Concluding, we expanded the knowledge on the activities of PTD-NO and PTD-OH by showing that these phthalimide analogs also exhibit marked activity in models of nociceptive and inflammatory pain and inflammatory edema. Opioid and cannabinoid mechanisms partially mediate the anti-inflammatory, but not the antinociceptive activity.
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Adriana M
authors: AM
authors: Godin
authors: Departamento de Química, Instituto de Ciências Exatas Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Débora P
authors: DP
authors: Araújo
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Isabela C
authors: IC
authors: César
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Raquel R
authors: RR
authors: Menezes
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Ana Mercy S
authors: AM
authors: Brito
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Ivo S F
authors: IS
authors: Melo
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Giovanna M E
authors: GM
authors: Coura
authors: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Leandro F S
authors: LF
authors: Bastos
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Mariana O
authors: MO
authors: Almeida
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Ricardo M D
authors: RM
authors: Byrro
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Tamires C
authors: TC
authors: Matsui
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Carla R A
authors: CR
authors: Batista
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Gerson A
authors: GA
authors: Pianetti
authors: Departamento de Química, Instituto de Ciências Exatas Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Ângelo
authors: Â
authors: de Fátima
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Renes R
authors: RR
authors: Machado
authors: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha CEP, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: mmcoelho@farmacia.ufmg.br.
authors: Márcio M
authors: MM
authors: Coelho
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004487:Edema / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D005557:Formaldehyde / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009292:Narcotic Antagonists / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D010797:Phthalimides / Q000494:pharmacology* / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors
chemical_list: C000604191:2-phthalimidethanol; C000604190:2-phthalimidethyl nitrate; D000700:Analgesics; D009292:Narcotic Antagonists; D010797:Phthalimides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D005557:Formaldehyde
keywords: 2-phthalimidethanol; 2-phthalimidethyl nitrate; Cannabinoid and opioid mechanisms; Inflammation; Pain