Modulatory effects of PLG and its peptidomimetics on haloperidol-induced catalepsy in rats
| Autor: | Rodney L. Johnson, Willard J. Costain, Margaret C. Evans, Adam T Buckley, Ram K. Mishra |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Physiology Peptidomimetic Pharmacology Catalepsy Biochemistry Haloperidol induced catalepsy Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Dopamine medicine Haloperidol Animals Dose-Response Relationship Drug Molecular Mimicry Dopaminergic medicine.disease MSH Release-Inhibiting Hormone Rats Mechanism of action chemistry Lactam medicine.symptom medicine.drug |
| Zdroj: | Peptides. 20:761-767 |
| ISSN: | 0196-9781 |
| DOI: | 10.1016/s0196-9781(99)00060-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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