Desipramine enhances the ability of paliperidone to decrease alcohol drinking
| Autor: | Alan I. Green, Jibran Y. Khokhar, Danielle Gulick, David T. Chau, Ree Dawson |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Alcohol Drinking medicine.drug_class Atypical antipsychotic Alcohol use disorder Pharmacology Choice Behavior Article Eating Random Allocation Species Specificity Norepinephrine reuptake inhibitor Desipramine Paliperidone Palmitate Animals Medicine Paliperidone Biological Psychiatry Clozapine Adrenergic Uptake Inhibitors Dose-Response Relationship Drug Ethanol Mesocricetus business.industry Drinking Water Body Weight Central Nervous System Depressants Drug Synergism Adrenergic alpha-2 Receptor Antagonists medicine.disease Rats Disease Models Animal Dopamine D2 Receptor Antagonists Psychiatry and Mental health Alcohol Deterrents business medicine.drug |
| Zdroj: | Journal of Psychiatric Research. 69:9-18 |
| ISSN: | 0022-3956 |
| Popis: | Alcohol use disorder commonly occurs in patients with schizophrenia and dramatically worsens their course. The atypical antipsychotic clozapine has been associated with reduced drinking in these patients, but its toxicity reduces its use. We have attempted to create a clozapine-like drug by combining agents that capture components of clozapine's pharmacologic action, including its weak dopamine D2 blockade and noradrenergic modulation. The current study assessed whether paliperidone, a dopamine D2 receptor and adrenergic alpha-2 receptor antagonist like clozapine, would attenuate alcohol drinking in the alcohol-preferring P rat and the Syrian golden hamster, and whether desipramine, a norepinephrine reuptake inhibitor, would potentiate the ability of paliperidone to attenuate alcohol drinking in the P rat and the Syrian golden hamster. Daily subcutaneous injections of paliperidone (5 mg/kg for the rat; 1 mg/kg for the hamster) over 20 days slightly and transiently attenuated initiation of alcohol consumption in both animals. Desipramine (3 mg/kg) or lower doses of paliperidone alone did not affect alcohol drinking. However, the combination of desipramine (3 mg/kg) and paliperidone essentially prevented initiation of alcohol drinking and acquisition of alcohol preference in the P rat (2.5 or 5 mg/kg), and almost as dramatically suppressed chronic alcohol intake and alcohol preference in the hamster (2.5 mg/kg). Taken together, the current data suggest that (1) the desipramine and paliperidone combination attenuates alcohol drinking in a synergistic manner, and (2) desipramine and paliperidone may serve as an effective new treatment for alcohol use disorder in patients with schizophrenia. |
| Databáze: | OpenAIRE |
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