Subeffective doses of nitroparacetamol (NCX-701) enhance the antinociceptive activity of the α2-adrenoceptor agonist medetomidine Original Research Article
Pharmacology Biochemistry and Behavior, Volume 99, Issue 3, September 2011, Pages 385-390
Carlos Molina, Juan F. Herrero
The α2-adrenergic system is involved in pain processing and inflammation-induced sensitization. α2-adrenoceptor agonists induce analgesia, and this effect is greater when administered in combination with other analgesics. In the present study, we assessed a possible enhancement of antinociception combining the α2-adrenoceptor agonist medetomidine with subeffective doses of NCX701 (nitroparacetamol). The effects of the drugs were studied in spinal cord neuronal responses from adult male Wistar rats with carrageenan-induced inflammation, using the recording of single motor unit technique. The experiments showed that the i.v. administration of medetomidine and NCX701 induced a more potent and effective antinociceptive effect than medetomidine when given alone (ID50: 0.47 ± 0.1 vs. 1.1 ± 0.1 μg/kg) or in the presence of paracetamol, in naturally-evoked nociceptive responses. In addition, the duration of antinociception was significantly longer (P < 0.001, 100 min after administration). The use of low doses of NCX701 and α2-adrenoceptor agonists might open new perspectives in the treatment of inflammatory pain.
A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy Original Research Article
Pharmacological Research, Volume 64, Issue 3, September 2011, Pages 210-217
Clara Sciorati, Daniela Miglietta, Roberta Buono, Viviana Pisa, Dario Cattaneo, Emanuele Azzoni, Silvia Brunelli, Emilio Clementi
A resolutive therapy for muscular dystrophies, a heterogeneous group of genetic diseases leading to muscular degeneration and in the severe forms to death, is still lacking. Since inflammation and defects in nitric oxide generation are recognized key pathogenic events in muscular dystrophy, we have analysed the effects of a derivative of ibuprofen, NCX 320, belonging to the class of cyclooxygenase inhibiting nitric oxide donator (CINOD), in the α-sarcoglycan null mice, a severe mouse model of dystrophy. NCX 320 was administered daily in the diet for 8 months starting 1 month from weaning. Muscle functional recovery was evaluated by free wheel and treadmill tests at 8 months. Serum creatine kinase activity, as well as the number of diaphragm inflammatory infiltrates and necrotic fibres, was measured as indexes of skeletal muscle damage. Muscle regeneration was evaluated in diaphragm and tibialis anterior muscles, measuring the numbers of centronucleated fibres and of myogenic precursor cells. NCX 320 mitigated muscle damage, reducing significantly serum creatine kinase activity, the number of necrotic fibres and inflammatory infiltrates. Moreover, NCX 320 stimulated muscle regeneration increasing significantly the number of myogenic precursor cells and regenerating fibres. All these effects concurred in inducing a significant improvement of muscle function, as assessed by both free wheel and treadmill tests. These results describe the properties of a new compound incorporating nitric oxide donation together with anti-inflammatory properties, showing that it is effective in slowing muscle dystrophy progression long term. Of importance, this new compound deserves specific attention for its potential in the therapy of muscular dystrophy given that ibuprofen is well tolerated in paediatric patients and with a profile of safety that makes it suitable for chronic treatment such as the one required in muscular dystrophies.