Comparative antipsychotic profiles of neurotensin and a related systemically active peptide agonist
| Autor: | Janice M Hitchcock, Christine Grauffel, Joseph G Wettstein, Shakir Sarhan |
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| Rok vydání: | 1997 |
| Předmět: |
Agonist
Male medicine.medical_specialty Physiology medicine.drug_class (+)-Naloxone Catalepsy Pharmacology Motor Activity Biochemistry Body Temperature Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Endocrinology Dopamine Internal medicine medicine Animals Receptors Neurotensin Amphetamine Phencyclidine Neurotensin Pain Measurement Analgesics Chemistry digestive oral and skin physiology Dopaminergic medicine.disease nervous system Oligopeptides hormones hormone substitutes and hormone antagonists medicine.drug Antipsychotic Agents |
| Zdroj: | Peptides. 18(8) |
| ISSN: | 0196-9781 |
| Popis: | Sarhan, S., J. M. Hitchcock, C. A. Grauffel and J. G. Wettstein. Comparative antipsychotic profiles of neurotensin and a related systemically active peptide agonist. Peptides 18(8) 1223–1227, 1997.—Several lines of evidence have shown that neurotensin can modulate dopamine neurotransmission. It has been suggested that neurotensin has potential antipsychotic activity because it reduces dopaminergic activity preferentially in the nucleus accumbens. In the present study, the effects of neurotensin and NT1 (N α Me-Arg-Lys-Pro-Trp-TIe-Leu or Eisai hexapeptide), a metabolically stable and systemically active neurotensin agonist, were examined in several models of antipsychotic activity and side effect liability in mice; analgesic and hypothermic effects of both compounds also were determined. Up to high doses, neurotensin (5.0 and 10.0 μg, ICV) and NT1 (10.0 and 20.0 mg/kg, IP) did not produce catalepsy. A much lower dose of neurotensin (0.03 μg, ICV) significantly reduced amphetamine- and phencyclidine-stimulated locomotor activity; NT1 also diminished amphetamine- and phencyclidine-stimulated locomotion with ED 50 values of 0.3 and 0.4 mg/kg, IP, respectively. Neurotensin (0.01–0.3 μg, ICV) and NT1 (0.1–1.0 mg/kg, SC) also produced dose-dependent analgesia in the paw pressure test and decreased body temperature; these effects were insensitive to pretreatment with naloxone (10.0 mg/kg, IP). Together, the results support the hypothesis that neurotensin agonists have antipsychotic and analgesic activity. Moreover, the data suggest that such compounds may not produce extrapyramidal side effects. |
| Databáze: | OpenAIRE |
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