title: New benzodiazepines alter acetylcholinesterase and ATPDase activities.
abstract: This study examines the effect of new 1,5 benzodiazepines on acetylcholinesterase (AChE) and ATPDase (apyrase) activities from cerebral cortex of adult rats. Simultaneously, the effects of the classical 1,4-benzodiazepine on these enzymes were also studied for comparative purpose. The compounds 2-trichloromethyl-4-phenyl-3H-1,5-benzodiazepin and 2-trichloromethyl-4(p-methyl-phenyl)-3H- 1,5-benzodiazepin significantly inhibited acetylcholinesterase activity (p < 0.01) when tested in the range of 0.18-0.35 mM. The inhibition caused by these two new benzodiazepines was noncompetitive in nature. Similarly, at concentrations ranging from 0.063 to 0.25 mM, the 1,5 benzodiazepines inhibited ATP and ADP hydrolysis by synaptosomes from cerebral cortex (p < 0.01). However, the inhibition of nucleotide hydrolysis was uncompetitive in nature. Our results suggest that, although diazepam and the new benzodiazepines have chemical differences, they both presented an inhibitory effect on acetylcholinesterase and ATPDase activities.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brasil. mrosa@base.ufsm.br
authors.forename: M R
authors.initials: MR
authors.lastname: Schetinger
authors.forename: N M
authors.initials: NM
authors.lastname: Porto
authors.forename: M B
authors.initials: MB
authors.lastname: Moretto
authors.forename: V M
authors.initials: VM
authors.lastname: Morsch
authors.forename: J B
authors.initials: JB
authors.lastname: da Rocha
authors.forename: V
authors.initials: V
authors.lastname: Vieira
authors.forename: F
authors.initials: F
authors.lastname: Moro
authors.forename: R T
authors.initials: RT
authors.lastname: Neis
authors.forename: S
authors.initials: S
authors.lastname: Bittencourt
authors.forename: H G
authors.initials: HG
authors.lastname: Bonacorso
authors.forename: N
authors.initials: N
authors.lastname: Zanatta
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000378:metabolism*; D001569:Benzodiazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001569:Benzodiazepines; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000110:Acetylcholinesterase; D001081:Apyrase