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Why benzodiazepines have a different onset of action?

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Renald

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Lets take alprazolam and clonazepam in panic attack situations. What is the basic mechanism, explaining why one drug acts more quickly via the same way comparing it to another similar drug?
 
Different drugs bind to different spots (different subtypes of GABAa receptors) and that can make a difference in the effects of different benzodiazepines too, but in table here it describes absorption of different benzos.
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0404.2008.01004.x/full#t1

I don't know how much absorption/half life issues come into play but that could be a factor too, I thought clonazepam has a very long half life so maybe it's not as instant release absorption/metabolism wise? Lipophilicity is important when concerning drugs passing the into the brain and that could be different as well. Idk, hope this helps.
 
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Actually i do't think it has anything to do with that. I could be wrong but i think Alprazolam just kicks in faster and just lasts alot shorter compared to Clonazepam. I didn't find method of administration to make a difference either because when i got vials of Lorazepam and ampules of Valium the only difference was a faster onset when IVed but it still lasted as long and wasn't stronger either.
 
Seems to be a function of lipophilicity, in other words how well a drug dissolves in fat / fatty tissues. That determines how well it passes BBB (or how it is distributed and retained).
Even if a benzo has a long half life, if it is very lipophilic like alprazolam and diazepam it has a relatively fast onset of action but short clinical duration (of course for diazepam it is still damn long).

Paranoid Android: I think your observations are explained by other factors that determine bioavailability and related to that the potency difference when comparing routes of administration.
 
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Agree with clubcard and others; logP for it to cross the BBB. Guessing the closed ring form has a more optimum logP so pka would also matter.

I think another thing which has been overlooked here is absorption into the bloodstream itself. This could be affected by a variety of things eg tablet formulations and binders which will physically delay the pill from breaking up.

Other factors depending on the individual includes how full/empty the stomach is and the individual's GI tract itself (could be slightly different in different people). I'd say these factors are quite significant as well; there's a massive variance in how long it takes for people to come up who take the exact same pill, and that could be due to these factors.
 
There are a HOST of 1,5-benzodiazepines waiting in the wings. Different receptor junction so no problem. Possible to make the triazolo derivatives (or at least they are patented). I guess 7-nitro-'2-fluoro would be potent enough.
 
The ampoules will probably be prepped. I thought propylene glycol was the preferred solvent for IV infusion?
 
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