A novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline inhibits nociception and oedema in mice

作者：Bastos L F S; Angusti A; Vilaca M C; Merlo L A; Nascimento E B Jr; Rocha L T S; Godin A M; Solano A G R; Jarussophon S; Nunan E A; Konishi Y; Coelho M M^*

来源：British Journal of Pharmacology, 2008, 155(5): 714-721.

DOI：10.1038/bjp.2008.303

• minocycline
• 12S-hydroxy-1,12-pyrazolinominocycline
• chemically modified tetracyclines
• cylinder-plate assay
• chelating activity
• nociception
• pain
• oedema
• inflammation

Background and purpose: Many in vitro and fewer in vivo studies have shown that tetracyclines present anti-inflammatory activity. We investigated if a novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline, 12S-hydroxy-1,12- pyrazolinominocycline (PMIN), also induced antinociceptive and anti-inflammatory effects.
Experimental approach: Antibacterial effects against a minocycline-sensitive Staphylococcus aureus strain were evaluated by applying a cylinder-plate agar diffusion technique. Antibacterial effects of diluted serum from mice pre-treated with minocycline or PMIN were also evaluated. Ca(2 ) binding activity was assessed by spectrophotometry. Formalin-induced nociceptive responses and carrageenan-induced paw oedema were evaluated in mice. The rota-rod apparatus was used to evaluate motor coordination.
Key results: Minocycline, but not PMIN, inhibited bacterial growth. Serum from mice treated with minocycline, but not with PMIN, also induced such an effect. The UV absorption spectrum of solutions of minocycline, but not those of PMIN, was markedly changed in the presence of Ca(2 ). Minocycline or PMIN inhibited both phases of formalin-induced nociception and carrageenan-induced paw oedema. It is unlikely that antinociception resulted from lack of motor coordination, as tetracycline did not impair the performance of mice on the rotating rod.
Conclusions and implications: These results indicate that inhibition of nociception and oedema by tetracyclines is neither necessarily linked to antibacterial nor to Ca(2 ) chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the treatment of painful and inflammatory diseases, as its lack of antibacterial and Ca(2 ) chelating activities might confer greater safety over conventional tetracyclines.

• 出版日期2008-11