Nantenine and papaverine differentially modify synaptosomal membrane enzymes.
Papaverine (1-[(3,4-Dimethoxyphenyl) methyl]-6,7-dimethoxyisoquinoline) and nantenine (O-methyldomesticine) are chemically related isoquinoline alkaloids displaying similar dose-dependent sedative or convulsant effects, but seem to act differentially on synaptosomal membrane enzymes. Na+, K+-, Mg2+- and Ca2+-ATPase activities were inhibited by nantenine but not by papaverine, whereas acetylcholinesterase activity remained unchanged by nantenine but slightly enhanced by papaverine. Nantenine inhibited roughly both 20-50% Ca2+- and Mg2+-ATPase activities but 40-90% Na+, K+-ATPase activity. Kinetic analysis indicated that nantenine interacts with the substrate ATP for Ca2+-ATPase activity but that it competes with K+ for Na+, K+-ATPase activity. Given the roles of Na+, K+-ATPase and Ca2+-ATPase in cation transport and [Ca2+]i regulation, respectively, the inhibitory effect of nantenine upon these enzymes may explain its convulsant effect though not its sedative activity. The sedative action of both nantenine and papaverine is hardly attributable to an effect on the synaptosomal membrane enzymes assayed.
Ribeiro
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Departamento de Farmacologia, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
Rodríguez de Lores Arnaiz
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D000110:Acetylcholinesterase / Q000187:drug effects; D000251:Adenosine Triphosphatases / Q000187:drug effects*; D000818:Animals; D001060:Aporphines / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010208:Papaverine / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
D001060:Aporphines; D002491:Central Nervous System Agents; D003292:Convulsants; D006993:Hypnotics and Sedatives; D010936:Plant Extracts; D010208:Papaverine; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; C041615:nantenine