| Registro completo |
| Provedor de dados: |
BJMBR
|
| País: |
Brazil
|
| Título: |
Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
|
| Autores: |
Silva,G.A.P.
Kummerle,A.E.
Antunes,F.
Fraga,C.A.M.
Barreiro,E.J.
Zapata-Sudo,G.
Sudo,R.T.
|
| Data: |
2013-03-01
|
| Ano: |
2013
|
| Palavras-chave: |
N-acylhydrazone
Locomotor activity
Sedation
Hypnosis
Benzodiazepine receptor
Flumazenil
|
| Resumo: |
The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg,ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg,ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.
|
| Tipo: |
Info:eu-repo/semantics/article
|
| Idioma: |
Inglês
|
| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000300263
|
| Editor: |
Associação Brasileira de Divulgação Científica
|
| Relação: |
10.1590/1414-431X20122085
|
| Formato: |
text/html
|
| Fonte: |
Brazilian Journal of Medical and Biological Research v.46 n.3 2013
|
| Direitos: |
info:eu-repo/semantics/openAccess
|
|
