Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide.
BACKGROUND
Linalool oxide (OXL) (a monoterpene) is found in the essential oils of certain aromatic plants, or it is derived from linalool. The motivation for this work is the lack of psychopharmacological studies on this substance.


OBJECTIVE
To evaluate OXL's acute toxicity, along with its anticonvulsant and antinociceptive activities in male Swiss mice.


METHODS
OXL (50, 100 and 150 mg/kg, i.p.) was investigated for acute toxicity and in the Rota-rod test. Antinociceptive activity was evaluated by the acetic acid-induced writhing test, and by formalin testing. Anticonvulsant effects were demonstrated by testing for pentylenetetrazol (PTZ)-induced seizures and by Maximum Electroshock headset (MES) test. OXL was administered to the animals intraperitoneally 30 min before for pharmacological tests.


RESULTS
OXL showed an LD50of ∼721 (681-765) mg/kg. In the Rota-rod test, it was observed that OXL caused no damage to the animal's motor coordination. OXL significantly reduced (p < .001) the number of writhings. OXL also significantly decreased (p < .05, p < .01 or p < .001) paw-licking time in the two phases of the formalin test. OXL significantly reduced (p < .01 or p < .001) the duration of tonic seizures in the MES test, and at the dose 150 mg/kg, significantly increased (p < .01) the latency to first seizure in the PTZ test.


CONCLUSIONS
The tested doses of OXL were safe, with no motor impairment, and show clear antinociceptive and anticonvulsant potential. Future investigations with this monoterpene may lead to the development of a new molecule with even higher potency and selectivity.
a Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB) , Federal University of Paraíba (UFPB) , João Pessoa , Paraíba , Brazil.
Flávia Negromonte
FN
Souto-Maior
a Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB) , Federal University of Paraíba (UFPB) , João Pessoa , Paraíba , Brazil.
Diogo Vilar da
DV
Fonsêca
a Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB) , Federal University of Paraíba (UFPB) , João Pessoa , Paraíba , Brazil.
Paula Regina Rodrigues
PR
Salgado
a Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB) , Federal University of Paraíba (UFPB) , João Pessoa , Paraíba , Brazil.
Lucas de Oliveira
LO
Monte
a Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB) , Federal University of Paraíba (UFPB) , João Pessoa , Paraíba , Brazil.
Damião Pergentino
DP
de Sousa
a Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB) , Federal University of Paraíba (UFPB) , João Pessoa , Paraíba , Brazil.
Reinaldo Nóbrega
RN
de Almeida
D019342:Acetic Acid; D000080462:Acyclic Monoterpenes; D000700:Analgesics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects*; D003511:Cyclohexanols / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005557:Formaldehyde; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology* / Q000633:toxicity; D009043:Motor Activity; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D010433:Pentylenetetrazole; D011930:Reaction Time / Q000187:drug effects; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013997:Time Factors; D014320:Triphenylmethyl Compounds / Q000494:pharmacology* / Q000633:toxicity
D000080462:Acyclic Monoterpenes; D000700:Analgesics; D000927:Anticonvulsants; D003511:Cyclohexanols; D039821:Monoterpenes; D014320:Triphenylmethyl Compounds; D005557:Formaldehyde; C000593345:linalool oxide; D019342:Acetic Acid; D010433:Pentylenetetrazole
Pain; essential oil; nociception