Adenosine analogs attenuate tolerance-dependence on alprazolam.
1. Tolerance to and physical dependence on alprazolam were induced in mice by administering two doses of a slow release preparation. 2. Physical dependence was evaluated by the abstinence syndrome induced by flumazenil. Tolerance was studied by measuring the motor incoordination induced by a test dose of alprazolam. 3. The intensity of tolerance was decreased by the administration of L-phenylisopropyl adenosine (L-PIA), cyclopentyl adenosine (CPA), cyclohexyl adenosine (CHA), N-ethylcarboxamide adenosine (NECA), 8-phenyltheophylline (8-PTP) and theophylline (TP). 4. The intensity of the abstinence syndrome induced by flumazenil was attenuated by L-PIA, CPA NECA, TP and 8-PTP. 5. The results suggest that benzodiazepines may exert, at least in part, their effects by involving adenosine in the central nervous system.
Contreras
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Departamento de Farmacología, Facultad de Ciencias Biológicas y de Recursos Naturales, Universidad de Concepción, Chile.
Germany
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D000525:Alprazolam; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology; D008297:Male; D051379:Mice; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000503:physiopathology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D010660:Phenylisopropyladenosine; C027513:N(6)-cyclohexyladenosine; C048599:N(6)-cyclopentyladenosine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D000525:Alprazolam