Lyness_1979_Eur.J.Pharmacol_54_319

Reference

Title : Cross-tolerance to centrally injected barbiturates - Lyness_1979_Eur.J.Pharmacol_54_319
Author(s) : Lyness WH , Brezenoff HE , Mycek MJ
Ref : European Journal of Pharmacology , 54 :319 , 1979
Abstract :

Hypnotic responses to intracerebroventricular (i.c.v) injections of either barbital, pentobarbital, R(-) and S(+) mephorbarbital, or racemic metharbital were compared to those produced by phenobarbital. Dose--response relationships were obtained for all except S(+) mephorbarbital and metharbital. Chronic i.c.v. phenobarbital administration resulted in tolerance to the drug's hypnotic effects. However, chronic barbital administration using an identical regimen did not produce tolerance, nor were phenobarbital tolerant rats cross-tolerant to barbital. Chronic i.c.v pentobarbital resulted in an irreversible decrease in responsiveness to its own effects and to those of other barbiturates. This was attributed to the high alkalinity of the solution (pH 9.6) since i.c.v. injection of saline adjusted to the same pH also reduced responsiveness to i.c.v. barbiturates. However, rats tolerant to i.c.v. phenobarbital were tolerant to acute i.c.v. injection of pentobarbital. Similar cross-tolerance was observed on systemic administration of the barbiturates. The efflux rates of i.c.v. phenobarbital or barbital and their distribution to different brain areas were identical in tolerant and nontolerant rats. Awakening phenobarbital brain levels of the tolerant rats were approximately three times higher than those in nontolerant controls. The conclusion is reached that central administration of phenobarbital provides a valid model for studying functional tolerance.

PubMedSearch : Lyness_1979_Eur.J.Pharmacol_54_319
PubMedID: 436931

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Citations formats

Lyness WH, Brezenoff HE, Mycek MJ (1979)
Cross-tolerance to centrally injected barbiturates
European Journal of Pharmacology 54 :319

Lyness WH, Brezenoff HE, Mycek MJ (1979)
European Journal of Pharmacology 54 :319