Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives
| Autor: | Stela Maris Kuze Rates, Carlos A. M. Fraga, E.J. Barreiro, Leandro Tasso, Gilda Neves, Alice Fialho Viana, Ana Paula Machado Heckler, Raquel Fenner, Ricardo Menegatti, T. Dalla-Costa |
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| Předmět: |
Male
Piperazinas Time Factors Physiology Dopamine Immunology Biophysics Dopamina Context (language use) Hypothermia Pharmacology Catalepsy Amphetamine stereotypy Biochemistry Piperazines Mice Structure-Activity Relationship Apomorphine hypothermia medicine Haloperidol Animals General Pharmacology Toxicology and Pharmaceutics Rats Wistar Amphetamine lcsh:QH301-705.5 Psicofarmacologia lcsh:R5-920 Psychotropic Drugs Chemistry General Neuroscience Dopaminergic Cell Biology General Medicine Triazoles medicine.disease Rats Apomorphine Stereotypy (non-human) lcsh:Biology (General) N-phenylpiperazine derivatives Anesthesia Dopamine Antagonists Pyrazoles Stereotyped Behavior lcsh:Medicine (General) medicine.drug |
| Zdroj: | Scopus-Elsevier Brazilian Journal of Medical and Biological Research, Volume: 36, Issue: 5, Pages: 625-629, Published: MAY 2003 Brazilian Journal of Medical and Biological Research, Vol 36, Iss 5, Pp 625-629 (2003) Repositório Institucional da UFRGS Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS |
| Popis: | Dopamine constitutes about 80% of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors. |
| Databáze: | OpenAIRE |
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