Posted by chemist on May 18, 2004, at 15:59:43
In reply to Re: Chemist...questionChemist » chemist, posted by chess on May 18, 2004, at 14:39:19
you asked if K is hitting fewer GABA receptors with respect to time or if the same receptors were being hit but with lower ``strength:'' it is the latter that is closest to the correct answer. the presence of a more lipophilic derivative of K (the result of miking a nitro group into a primary amino group in the 7 position) - which is pharmacologically active - means that this metabolite will stay around in the brain longer, and i am not aware of any change in specificity for the BZD site in the GABA type A receptor.
the blood/brain barrier is where hydrophilic moieties hit the lipophilic wall, and the answer to whether hydrophilic and lipophilic compounds cross is yes, but you can see that a hydrophilic drug will be transported more quickly to the BBB than a hydrophobic one BUT we have to consider that if a lipophilic drug hitches a ride by being partitioned into a carrier that is itself hydrophilic, then the lipophilic drug can reach the BBB quite quickly and cross quite quickly (this is why, in prn dosing, diazepam has a quicker onset than does lorazepam, due to the extreme hydrophobicity of diazepam and the albeit slight hydrophilicity of lorazepam, not to mention the slightly increased hydrophilicity of nordiazepam and oxazepam, 2 of the active metabolites of diazepam). and yes, clonazepam is lipophilic on the whole, but the presence of the nitro group (which becomes an animo group upon metabolism) does make it somewhat hydrophilic....hope this helps, all the best, chemist
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thread:347588
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