Effect on brain monoamines in the rat of substituted and protected analogues of the oxytocin fragment, prolyl-leucyl-glycinamide following N-terminal substitution by homoproline.
Prolyl-leucyl-glycinamide (PLG) and its substituted and protected analogues were tested on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain areas. The tripeptides were structurally modified at the N-terminal proline residue either by protection with benzoxycarbonyl (Z group) or by tertiary butyroxycarbonyl (BOC), or by substitution with homoproline (HPRO). C-terminal modification was performed by substitution of the amino group of glycine (GLY-NH2) by methylester (GLY-OMe). The parent molecule (PLG) increased the 5-HT content in the striatum and the NA and DA levels in the dorsal hippocampus. N-terminal protection by Z-group resulted in a loss of these effects. Striatal effects re-appeared if a methylester group was introduced in the C-terminal glycine. Substitution of the N-terminal with HPRO or that of the C-terminal amine group by OMe resulted in a tendency to increase the 5-HT level in the hypothalamus.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects
D012701:Serotonin; D009075:MSH Release-Inhibiting Hormone; D011392:Proline; C010983:homoproline; D004298:Dopamine; D009638:Norepinephrine