Effects of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine diastereomers on monoamine uptake and monoamine oxidase in rat brain.
The diastereomers of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2 R, 3 R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2 S, 3 S)-TPP was least potent. In contrast, the (2 S, 3 S)- and (2 S, 3 R)-diastereomers of TPP were more potent than (2 R, 3 R)- and (2 R, 3 S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S)-configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake.
Smith
D F
DF
Psychopharmacology Research Unit, Psychiatric Hospital, Risskov, Denmark.
Jensen
P N
PN
Gelbcke
M
M
Tytgat
D
D
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015306:Biogenic Monoamines; D010879:Piperazines; D008995:Monoamine Oxidase