Abstract
A behavioral model of dopaminergic function in the rat was used to examine the anticataleptic effects of L-prolyl-L-leucyl-glycinamide (PLG) and peptidomimetic analogs of PLG. Administration of 1 mg/kg PLG intraperitoneally significantly attenuated haloperidol (1 mg/kg)-induced catalepsy (as measured by the standard horizontal bar test), whereas doses of 0.1 and 10 mg/kg PLG did not. Eight synthetic PLG peptidomimetics (Cα, α-dialkylated glycyl residues with lactam bridge constraint [1-4] and without [5-8]) were tested in the same manner (at a dose of 1 μg/kg) and categorized according to their activity, i.e. very active (5), moderately active (2, 3, 4, and 6), and inactive (1, 7, and 8). The catalepsy-reversal action of the diethylglycine-substituted peptidomimetic 5 was examined further and found to exhibit a U-shaped dose-response effect with an optimal dose of 1 μg/kg. The similarity between the effects of PLG and the synthetic peptidomimetics suggests a common mechanism of action. Finally, the synthetic peptidomimetics examined here, particularly peptidomimetic 5, were more effective than PLG in attenuating haloperidol-induced catalepsy. Copyright (C) 1999 Elsevier Science Inc.
Original language | English (US) |
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Pages (from-to) | 761-767 |
Number of pages | 7 |
Journal | Peptides |
Volume | 20 |
Issue number | 6 |
DOIs | |
State | Published - Aug 1999 |
Bibliographical note
Funding Information:This work was supported by NIH Grant NS20036–11. W.J.C. is a recipient of a PMAC-MRC predoctoral fellowship.
Keywords
- Catalepsy
- Dopamine
- Haloperidol
- PLG
- Parkinson's disease
- Peptidomimetic
- Schizophrenia