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Pharmacological modulation of abnormal involuntary DOI-induced head twitch response movements in male DBA/2J mice: II. Effects of D3 dopamine receptor selective compounds.
Rangel-Barajas, Claudia; Malik, Maninder; Mach, Robert H; Luedtke, Robert R.
Afiliación
  • Rangel-Barajas C; University of North Texas Health Science Center, Department of Pharmacology and Neuroscience, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
  • Malik M; University of North Texas Health Science Center, Department of Pharmacology and Neuroscience, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
  • Mach RH; Radiochemistry Laboratory, Neurology Department, University of Pennsylvania School of Medicine, Chemistry Building, 231 S. 34th Street, Philadelphia, PA 19104, USA.
  • Luedtke RR; University of North Texas Health Science Center, Department of Pharmacology and Neuroscience, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA. Electronic address: robert.luedtke@unthsc.edu.
Neuropharmacology ; 93: 179-90, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25698528
We recently reported on the characterization of the hallucinogen 2,5-dimethoxy-4-methylamphetamine's (DOI) ability to elicit a head twitch response (HTR) in DBA/2J mice and the ability of D2 vs. D3 dopamine receptor selective compounds to modulate that response. For these studies, the ability of D3 vs. D2 dopamine receptor selective compounds to attenuate the DOI-dependent HTR was examined. WC 10, a D3 dopamine receptor weak partial agonist with 40-fold binding selectivity for D3 vs. D2 dopamine receptors, produced a dose-dependent decrease in the DOI-induced HTR (IC50 = 3.7 mg/kg). WC 44, a D3 receptor selective full agonist, also inhibited the DOI-induced HTR (IC50 = 5.1 mg/kg). The effect of two D3 receptor selective partial agonists, LAX-4-136 and WW-III-55, were also evaluated. These analogs exhibit 150-fold and 800-fold D3 vs. D2 binding selectivity, respectively. Both compounds inhibited the HTR with similar potency but with different maximum efficacies. At 10 mg/kg WW-III-55 inhibited the HTR by 95%, while LAX-4-136 administration resulted in a 50% reduction. In addition, DOI (5 mg/kg) was administered at various times after LAX-4-136 or WW-III-55 administration to compare the duration of action. The homopiperazine analog LAX-4-136 exhibited greater stability. An assessment of our test compounds on motor performance and coordination was performed using a rotarod test. None of the D3 dopamine receptor selective compounds significantly altered latency to fall, suggesting that these compounds a) did not attenuate the DOI-dependent HTR due to sedative or adverse motor effects and b) may have antipsychotic/antihallucinogenic activity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Agonistas de Dopamina / Movimientos de la Cabeza / Receptores de Dopamina D3 / Trastornos del Movimiento Tipo de estudio: Etiology_studies Límite: Animals / Humans / Male Idioma: En Revista: Neuropharmacology Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Agonistas de Dopamina / Movimientos de la Cabeza / Receptores de Dopamina D3 / Trastornos del Movimiento Tipo de estudio: Etiology_studies Límite: Animals / Humans / Male Idioma: En Revista: Neuropharmacology Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido