A testował ktoś branie antagonist NMDAr łącznie z benzo, aby zapobiec powstawaniu tolerki?
Lub antagonist NMDAr po odstawce, aby zapobiec symptomom odstawiennym?
"Pretreatment with either MK-801 or ketamine blocked tolerance to chlordiazepoxide-induced
motor impairment in rats tested on the tilt plane test, but this effect was dependent
on the dose ratio of the NMDA antagonist to that of the benzodiazepine (45). Thus, this
blockade was observed only when relatively low doses of chlordiazepoxide were used.
When a higher dose of this drug was used, MK-801 or ketamine failed to block chlordiazepoxide tolerance.
File and Fernandes (22), reported that pretreatment with
MK-801 blocked tolerance to the decrease in the number of head dips, and probably to the
decrease in ambulation produced by diazepam
in rats tested in the hole-board apparatus.
The development of tolerance to the locomotor activity reduction induced by diazepam
mice was prevented by treatment with the NMDA antagonist CPP
After 14 d of lorazepam
administration complete tolerance
to its anticonvulsant effect developed. The concomitant administration of CPP and
resulted in partial blockade of tolerance to the seizure protective effect of
benzodiazepines (61). Chronic administration of lorazepam
caused a significant reduction
in in vivo binding of [3H]flumazenil in cerebellum, hippocampus and hypothalamus. This
reduction was not affected by the simultaneous treatment with CPP, suggesting that the behavioral
effect of the NMDA antagonist was not directly related to the downregulation of
https://onlinelibrary.wiley.com/doi/pdf ... .tb00096.x
Wygląda na to, że takie działanie w zależności od dawek zapobiega powstawaniu tolerki na pewnych poziomach, ale nie zapobiega downregulacji receptora, chociaż inne badanie na szczurach mówi co innego, o ile prawidłowo to rozkminiam.
"The development of tolerance to and dependence on diazepam
was prevented by concurrent treatment of mice with CPP [antagonista NMDAr] but was not prevented by GYKI 52466. [antagonista AMPAr]"
Co prawda badania na szczurach i myszach... ale może jednak?