2-Bromoterguride-a potential atypical antipsychotic drug without metabolic effects in rats.
Rationale: Recently, we showed that 2-bromoterguride acted as a dopamine D receptor partial agonist, a serotonin 5-HT and α-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy. Objective: To extend our kno...
| Publicado en: | Psychopharmacology Vol. 233; no. 15/16; pp. 3041 - 3051 |
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| Autores principales: | , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Aug2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=116622651&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 116622651 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Aug2016 vid: 233 iid: 15/16 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 116622651 10.1007/s00213-016-4356-0 116622651 ppf: 3041 ppct: 10 formats: fmt: @attributes: type: P tig: atl: 2-Bromoterguride-a potential atypical antipsychotic drug without metabolic effects in rats. aug: au: Franke, Robert Tarland, Emilia Fink, Heidrun Pertz, Heinz Brosda, Jan affil: Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, 14195 Berlin Germany sug: ab: Rationale: Recently, we showed that 2-bromoterguride acted as a dopamine D receptor partial agonist, a serotonin 5-HT and α-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy. Objective: To extend our knowledge on the antipsychotic effects of 2-bromoterguride, we used convergent preclinical animal models and tests; i.e., conditioned avoidance response (CAR), predictive of antipsychotic-like effects; Fos protein expression, a molecular marker for (atypical) antipsychotic activity; wet dog shake behavior, a test for the in vivo effects of drugs acting on central 5-HT receptors; and investigated metabolic changes as a common side effect of atypical antipsychotic drugs (APDs). Results: Acute treatment with 2-bromoterguride (0.1 and 0.3 mg/kg) decreased the CAR at 30, 90, and 270 min post-injection in rats without inducing escape failures at any time. Fos protein expression, as shown by Western blotting, was enhanced by 2-bromoterguride in the nucleus accumbens (NAc), the dorsolateral striatum (dStr), and the medial prefrontal cortex (mPFC). (±)-2,5-Dimethoxy-4-iodoamphetamine (DOI)-induced wet dog shakes in rats were reduced by 2-bromoterguride. Chronic treatment with 2-bromoterguride did not affect metabolic parameters such as body weight development and body fat composition as well as behavioral parameters such as food intake and locomotor activity. Conclusions: Our data suggest that 2-bromoterguride is a promising candidate in the treatment of schizophrenia due to its atypical antipsychotic-like activity and its inability to induce weight gain. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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