Minocycline in leprosy patients with recent onset clinical nerve function impairment.

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy.

Antinociceptive properties of the ethanolic extract and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in mice.

The present study examined the antinociceptive effects of the ethanolic extract (EE) and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in chemical and thermal behavioural models of pain in mice. The EE (10-1000 mg/kg) given orally (p.o.), 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with mean ID50 value of 131.9 mg/kg. In the formalin test, the EE (10-300 mg/kg, p.o.) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, however, it was more potent and efficacious in relation to the late phase of the formalin test, with mean ID50 values for the neurogenic and the inflammatory phases of approximately 300 and 88.8 mg/kg, respectively. The EE (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of capsaicin- and glutamate-induced pain, with mean ID50 values of 160.5 and 38.3 mg/kg, respectively. Furthermore, the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene (1-30 mg/kg), given p.o., 1 h prior to testing, also produced dose-related inhibition of glutamate-induced pain, with a mean ID50 value of 5.6 mg/kg. When assessed in a thermal model of pain, the EE (10-300 mg/kg, p.o.) and fentanyl (100 microg/kg, s.c.) caused a significant and marked increase in the latency response on the hot-plate test (50 degrees C). The antinociception caused by EE (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with naloxone (opioid receptor antagonist, 1 mg/kg), pindolol (a 5-HT 1A/1B receptor/beta adrenoceptor antagonist, 1 mg/kg), WAY100635 (a 5-HT 1A receptor antagonist, 0.7 mg/kg) or ketanserin (a 5-HT 2A receptor antagonist, 0.3 mg/kg). In contrast, EE (100 mg/kg, p.o.) antinociception was affected neither by L-arginine (precursor of nitric oxide, 600 mg/kg) nor by ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg) i.p. treatment. It was not associated with non-specific effects such as muscle relaxation or sedation. Together, these results indicate that EE produces dose-related antinociception in several models of chemical and thermal pain through mechanisms that involve an interaction with opioid and serotonergic (i.e., through 5-HT 1A/1B and 5-HT 2A receptors) systems.

RO 15-1788 does not influence postpartum aggression in lactating female rats.

Recently, Hansen et al. (1985) suggested behavioural similarities between lactating rats and non-maternal rats treated with benzodiazepines (BDZ), indicating that lactation may be associated with an increased activity state at the GABA/BDZ receptor complex similar to BDZ treatment. A logical prediction of this hypothesis is that BDZ antagonists should decrease typical maternal behaviours involved, such as aggression. We tested this hypothesis by measuring the behavioural effects of the BDZ antagonist RO 15-1788 (1.25-10 mg/kg IP) on aggressive behaviour of lactating female rats confronted with male intruders. We could not support the hypothesis; no consistent behavioural effects of RO 15-1788 on aggression were found. The implications of this finding for the proposed hypothesis are discussed.