I would like to thoroughly explain cross-tolerance between various benzodiazepines, how it happens, and the difference between subunit tolerance and actual tolerance their selectivity for sub-units of the GABA-A receptor.
There are 6 different alpha sub-units at the GABA-A receptor. There are over 50 different benzodiazepines, and all of the have proven to only affect a1, a2, a3 and a5 sub-units. No binding affinity for the a4 and a6 receptor has been shown.
What are alpha sub-units and how do they affect the GABA-A receptor and your CNS?
Alpha sub-units increase the the frequency of the opening of "sensitivity to GABA" of the GABA-A receptor. To put this into simple words, they increase the amount of times GABA binds to the receptor.
The GABA-A receptor is structured randomly and the most common structure of it is 2 a1 receptors.
Benzodiazepines have high binding affinity for these sub-units, but effects can vary, depending on which of the sub-units it binds to.
a1 subunit: Responsible for sedation and amnesia. Benzos that are highly selective for this receptor, tend to be the most sedative.
Benzodiazepines that are know to be selective for this receptor:
Temazepam, Nitrazepam, Flubromazolam [citation needed], Triazolam, Phenazepam and Flunitrazepam.
Anectdotal experiences report that all of the benzos listed above are more euphoric than other benzos.
a2 and a3 subunit: Responsible for anxiolytic effects. Benzos that are highly selective for this receptor, tend to be best for anxiety relief.
Benzodiazepines that are known to be selective for this receptor:
Diazepam, Clonazepam, Bromazepam, Lorazepam, Alprazolam, Pyrazolam, Clonazolam [citation needed] and Gidazepam.
a5 subunit: Responsible for severe cognitive impairment. Benzos that are highly selective or that have noticeable selectivity for this receptor tend to cause the most severe cognitive impairment.
Benzodiazepines that are known to be selective for this receptor:
Highly selective: Triazolam, Flubromazolam [citation needed] and Phenazepam
Semi-selective: Alprazolam, Temazepam, Flunitrazepam and Nitrazepam.
Sub-unit tolerance. How it works and why it's different from regular tolerance. Also info on cross-tolerance.
Sub-unit tolerance consist of loss of sensitivity of that subunit to a certain dose of a benzo, while actual tolerance consist of "down regulation" of GABA-A receptor (aka physical dependance) which can only be gained through long term use, however extremely potent benzos with long half-lives can cause this much faster.
Though most benzos have cross-tolerance, some benzos have minimal cross-tolerance between each other. For example Temazepam and Flunitrazepam have very high cross tolerance, while Triazolam and Clonazepam have minimal cross-tolerance.
There are 6 different alpha sub-units at the GABA-A receptor. There are over 50 different benzodiazepines, and all of the have proven to only affect a1, a2, a3 and a5 sub-units. No binding affinity for the a4 and a6 receptor has been shown.
What are alpha sub-units and how do they affect the GABA-A receptor and your CNS?
Alpha sub-units increase the the frequency of the opening of "sensitivity to GABA" of the GABA-A receptor. To put this into simple words, they increase the amount of times GABA binds to the receptor.
The GABA-A receptor is structured randomly and the most common structure of it is 2 a1 receptors.
Benzodiazepines have high binding affinity for these sub-units, but effects can vary, depending on which of the sub-units it binds to.
a1 subunit: Responsible for sedation and amnesia. Benzos that are highly selective for this receptor, tend to be the most sedative.
Benzodiazepines that are know to be selective for this receptor:
Temazepam, Nitrazepam, Flubromazolam [citation needed], Triazolam, Phenazepam and Flunitrazepam.
Anectdotal experiences report that all of the benzos listed above are more euphoric than other benzos.
a2 and a3 subunit: Responsible for anxiolytic effects. Benzos that are highly selective for this receptor, tend to be best for anxiety relief.
Benzodiazepines that are known to be selective for this receptor:
Diazepam, Clonazepam, Bromazepam, Lorazepam, Alprazolam, Pyrazolam, Clonazolam [citation needed] and Gidazepam.
a5 subunit: Responsible for severe cognitive impairment. Benzos that are highly selective or that have noticeable selectivity for this receptor tend to cause the most severe cognitive impairment.
Benzodiazepines that are known to be selective for this receptor:
Highly selective: Triazolam, Flubromazolam [citation needed] and Phenazepam
Semi-selective: Alprazolam, Temazepam, Flunitrazepam and Nitrazepam.
Sub-unit tolerance. How it works and why it's different from regular tolerance. Also info on cross-tolerance.
Sub-unit tolerance consist of loss of sensitivity of that subunit to a certain dose of a benzo, while actual tolerance consist of "down regulation" of GABA-A receptor (aka physical dependance) which can only be gained through long term use, however extremely potent benzos with long half-lives can cause this much faster.
Though most benzos have cross-tolerance, some benzos have minimal cross-tolerance between each other. For example Temazepam and Flunitrazepam have very high cross tolerance, while Triazolam and Clonazepam have minimal cross-tolerance.
