Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

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.

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Main Authors: Silva,G.A.P., Kummerle,A.E., Antunes,F., Fraga,C.A.M., Barreiro,E.J., Zapata-Sudo,G., Sudo,R.T.
Format: Digital revista
Language:English
Published: Associação Brasileira de Divulgação Científica 2013
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000300263
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spelling oai:scielo:S0100-879X20130003002632015-10-08Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in miceSilva,G.A.P.Kummerle,A.E.Antunes,F.Fraga,C.A.M.Barreiro,E.J.Zapata-Sudo,G.Sudo,R.T. N-acylhydrazone Locomotor activity Sedation Hypnosis Benzodiazepine receptor Flumazenil 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.info:eu-repo/semantics/openAccessAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research v.46 n.3 20132013-03-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000300263en10.1590/1414-431X20122085
institution SCIELO
collection OJS
country Brasil
countrycode BR
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access En linea
databasecode rev-scielo-br
tag revista
region America del Sur
libraryname SciELO
language English
format Digital
author Silva,G.A.P.
Kummerle,A.E.
Antunes,F.
Fraga,C.A.M.
Barreiro,E.J.
Zapata-Sudo,G.
Sudo,R.T.
spellingShingle Silva,G.A.P.
Kummerle,A.E.
Antunes,F.
Fraga,C.A.M.
Barreiro,E.J.
Zapata-Sudo,G.
Sudo,R.T.
Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
author_facet Silva,G.A.P.
Kummerle,A.E.
Antunes,F.
Fraga,C.A.M.
Barreiro,E.J.
Zapata-Sudo,G.
Sudo,R.T.
author_sort Silva,G.A.P.
title Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
title_short Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
title_full Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
title_fullStr Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
title_full_unstemmed Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice
title_sort impairment of locomotor activity induced by the noveln-acylhydrazone derivatives lassbio-785 and lassbio-786 in mice
description 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.
publisher Associação Brasileira de Divulgação Científica
publishDate 2013
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000300263
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