Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of the inhalation of linalool oxide (0.65%, 1.25%, 2.5% and 5.0% w/w) in the elevated plus-maze and light/dark box tests as animal models of anxiety were investigated in adult male mice and compared with the effects of the reference anxiolytic diazepam (0.5 and 2.0 mg/kg), administered intraperitoneally. Additionally, the effects of inhaled linalool oxide were investigated in the rotarod test. Linalool oxide significantly increased the number of visits to the open arms of the elevated plus-maze and the amount of time spent there as well as the total number of entries. In the light/dark box test, inhalation of linalool oxide led to an increase in the time spent by the mice in the brightly-lit chamber and in the number of times the animal crossed from one compartment to another. Performance on the rotarod was unaffected. Thus, inhaled linalool oxide was found to have anxiolytic properties in both animal models, without causing any motor deficit. These results suggest that inhalation of linalool oxide may be a useful means of counteracting anxiety.

Nerolidol, an acyclic sesquiterpene found as a major constituent of several essential oils, has several pharmacological activities, but its action in pain processes has never been studied. The purpose of our research was to evaluate the antinociceptive and anti-inflammatory activities of nerolidol, as well as possible mechanisms of action, in experimental mouse models of pain. Antinociceptive activity was evaluated using the acetic acid-induced writhing test, the formalin test, and the hot-plate test. The nerolidol-treated group showed lesser acetic acid-induced abdominal contractions than the control group in all of the three doses tested (200, 300, and 400 mg/kg, p.o.). The formalin test doses of 300 and 400 mg/kg p.o. inhibited licking time, in both the first phase and the second phase. In the hot-plate test, nerolidol did not alter latency at any of the observed time points. Motor coordination, evaluated through the rotarod test, was not hindered in animals treated with nerolidol. Regarding the mechanism of action, the antinociceptive activity of nerolidol is related to the GABAergic system, and not to the opioidergic or ATP-sensitive K(+) channels. Treatment with nerolidol reduced carrageenan-induced paw edema. In the model of carrageenan-induced peritonitis, nerolidol decreased the influx of polymorphonuclear cells and also reduced levels of tumor necrosis factor (TNF-α) in peritoneal lavage. Nerolidol reduced production of interleukin 1 beta (IL-1β) in LPS-stimulated, peritoneal macrophages. Thus, these results showed that nerolidol has antinociceptive activity with possible involvement of the GABAergic system, and anti-inflammatory activity, attributed to the suppression of TNF-α and IL-1β proinflammatory cytokines.

Imidazolidine derivatives, or hydantoins, are synthetic compounds with different therapeutic applications. Many imidazolidine derivatives have psychopharmacological properties, such as phenytoin, famous for its anticonvulsant efficacy, but also effective in the treatment of neuropathic pain. The hydantoin, 3-phenyl-5-(4-ethylphenyl)-imidazolidine-2,4-dione (IM-3), synthesized from the amino acid, glycine, was selected for psychopharmacological studies in mice on the basis of its chemical and structural similarity with phenytoin. The first step of this study was to define the LD50, which determined the doses of 50, 100 and 200 mg/kg for subsequent tests. The results obtained from the behavioral screening indicated that IM-3 produces decreased ambulation and analgesia in mice. Motor coordination and anxiety behavior were not affected by treatment with IM-3, as observed in the rotarod and elevated plus-maze tests, respectively. Regarding its antinociceptive properties, IM-3 showed efficacy in the acetic acid-induced writhing test by OPEN ACCESSMolecules 2015, 20 975 increasing the latency of the first writhe and reducing the number of writhes, as well as reducing the paw licking time in the second phase of the formalin test. The behavior of treated animals exposed to the hot plate test, however, did not differ from that of the control group. These data suggest that IM-3 has antinociceptive effects in mice, which is probably mediated by anti-inflammatory mechanisms.

Acute treatment with the chloroform fraction of Dioclea virgata (Rich.) Amshoff (CFDv) in mice produced decreased ambulation and sedation in the behavioral pharmacological screening. Doses of 125 and 250 mg/kg CFDv decreased latency of sleep onset in the test of sleeping time potentiation. In the open field, animals treated with CFDv reduced ambulation and rearing (250 mg/kg), as well as defecation (125; 250 mg/kg). Regarding the antinociceptive activity, CFDv (125, 250, 500 mg/kg) increased latency to first writhing and decreased the number of writhings induced by acetic acid. In the formalin test, CFDv (250 mg/kg) decreased paw licking time in the first and second phases indicating antinociceptive activity that can be mediated both peripherally and at the central level. CFDv did not affect motor coordination until 120 minutes after treatment. CFDv shows psychopharmacological effects suggestive of CNS-depressant drugs with promising antinociceptive activity.