K'd-OUT-in-AZ
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The basics of Benzodiazepines. I spent various days during my days off putting this up via personal knowledge and looking up literature. Some copy and paste as well. There is much more stuff up that you can't just look up on benzo.org. If you have the time & interested in benzodiazepines please check this out, I'll feel this wasn't written in vain.
Some history of benzodiazepines… Chlordiazepoxide was the first benzodiazepine to be synthesized and its discovery was by pure chance. It was synthesized in the mid 1950's from work on a chemical dye, quinazolone-3-oxides. It was discovered by accident when in 1957 tests revealed that the compound had hypnotic, anxiolytic and muscle relaxant effects. Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. In 1963 diazepam hit the market under the brand name Valium, as a "simplified" version of chlordiazepoxide, primarily to counteract anxiety symptoms. The most positive results were observed among alcoholic patients. Sleep-related problems were treated with Nitrazepam (Mogadon), which was introduced in 1965, Temazepam (Restoril), which was introduced in 1969, and Flurazepam (Dalmane), which was introduced in 1973.
The molecular mechanisms of Benzodiazepines are well defined in that they enhance the actions of the inhibitory neurotransmitter GABA by binding to specific recognition sites on GABA-a receptors containing six discrete GABA-a (alpha) subunits, GABA alpha1-6. Of those six receptors, benzodiazepines have no affinity for (a 4) and (a 6). Compounds that bind at these modulator sites by enhancing the inhibitory actions of GABA are classified as agonists, those that decrease the actions of GABA are termed inverse agonists whereas compounds that counteract the effects are called antagonists. Flumazenil is a benzodiazepine antagonist that counteracts overdose.
The benzodiazepines represent a large class of drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties. They are potent anticonvulsants and have life-saving properties in the acute management of status epilepticus. There are over 50 known worldwide. These include the variants of the 1,4-benzodiazepines such as the prototype forms diazepam and nordiazepam (also known as nordazepam or N-desmethyl diazepam). Known 3-hydroxy metabolites, namely temazepam, lorazepam and oxazepam, are also registered as benzodiazepines in their own right. The majority of these drugs are excreted as glucuronide conjugates at the 3-hydroxy. Some drugs are metabolized to nordiazepam. These include chlordiazepoxide and clorazepate. 7-Nitro substituted 1,4-benzodiazepines such as
flunitrazepam, nitrazepam, and clonazepam represent a sub-group of drugs that are often abused. These 7-nitro substituted drugs are metabolized by nitroreduction and have no active metabolites. The triazolo ring type benzodiazepines are frequently very potent
and require much lower doses than the older analogs. Some examples include alprazolam, estazolam, and triazolam.
The five various benzodiazepine compounds:
2-Keto Compound
*Includes Diazepam, Flurazepam, Chlordiazepoxide
*All have active metabolites (Most commonly desmethyldiazepam)
*Longest active half-lives (Accumulates from repeated use. Anywhere from 20-200 hours)
3-hydroxy Compound
*Includes Lorazepam, Temazepam, Oxazepam
*No active metabolites
*Intermediate half-lives (generally 8-20 hours)
Triazolo
*Includes Alprazolam, Triazolam, Estazolam
*Few metabolites
*Very short half-lives (anywhere from 3-18 hours)
Imidazo
*Includes Midazolam, Loprazolam and antagonist Flumazenil
*Very potent water-soluble amnesiac sedatives with exception of Flumazenil which is an antagonist, used for overdose in intravenous formulation.
*Short to ultra short half-lives (7 hours or less; Flumazenil roughly 15-30 minutes)
7-Nitro Compound
*Includes Clonazepam, Nitrazepam, Flunitrazepam
*No active metabolites. Metabolized by nitroreduction
*Long half-lives (18-50 hours)
The binding properties and action of benzodiazepines depend on the alpha-subunit profile of the hetero-pentameric receptors: whereas the alpha1 subunit is associated with benzodiazepine type I (BZD1) pharmacology and reportedly mediates sedative as well as amnesic actions of benzodiazepines, the alpha2 subunit confers benzodiazepine type II (BZD2) pharmacology and mediates the anxiolytic actions of benzodiazepines.
All benzodiazepine agonists exert five primary effects and they are:
1. Hypnotic
(Prescribed for: short-term management of insomnia)
2. Anxiolytic
(Prescribed for: treatment of anxiety disorders and phobias; prevention of panic attacks)
3. Anti-convulsant/anti-seizure
(Prescribed for: seizure control; management of status epileptics; prevention of panic attacks)
4. Antispasmodic (Muscle relaxant)
(Prescribed for: treatment of muscle spasms, for example, Tetanus or spastic disorders and Restless legs syndrome.
5. Amnesic
Used as sedatives for patients receiving mechanical ventilation, or those in extreme distress or severe pain. Midazolam is the most common and effective for sleep-induced procedures.
Different benzodiazepines exhibit these primary effects to varying degrees. For example, diazepam (Valium) is a relatively powerful hypnotic, whereas the more modern benzodiazepines such as alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin) are less powerful hypnotics, but are very powerful anxiolytics. Do not assume that because one benzodiazepine makes you sleepier than another that this benzodiazepine is more potent than those that don’t produce sleepiness to the same degree. Often, the reverse is true.
The pharmacological spectrum of benzodiazepine site ligands, ranging from the therapeutic benefits of hypnosis, anxiolysis, anticonvulsant, and muscle relaxation to the potentially unwanted aspects of impaired motor co-ordination, attention and memory, tolerance and dependence and potentiation of the effects of alcohol, are believed to result from interactions with multiple GABA-A receptor “subunits”.
There are six GABA-a subunits, GABA(a 1), GABA(a 2), GABA(a 3), GABA(a 4), GABA(a 5) and GABA(a 6). Of those six receptors, benzodiazepines have no affinity for (a 4) and (a 6). Most effective anti-anxiety benzodiazepines have affinity to both alpha1 and alpha2 subunits while the more effective hypnotics have higher affinity to just the alpha1 subunit
GABA-A receptor subtype containing:
Alpha1: sedation, amnesiac, alcohol interaction, tolerance
Alpha2: anxiolysis, muscle relaxation
Alpha3: anxiolysis, muscle relaxation, sedation
Alpha5: memory, tolerance
The classical benzodiazepine show no selectivity between these GABA-A receptor subtypes and can exhibit the entire spectrum of pharmacological effects, depending on the dose. The “non-benzodiazepines” (zolpidem and zaleplon) show selectivity towards alpha1-containing GABA-A receptors, and these produce a predominant hypnotic pharmacological profile.
The alpha1-containing has been proposed to be responsible for the sedative action; the alpha2 and/or the alpha3 subtypes have been suggested to mediate the anxiolytic activity and the myorelaxation effects, and the alpha5 subtype has been associated with cognition processes.
The anticonvulsant properties of benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.
Primarily Anxiolytic Benzodiazepines: diazepam, clonazepam, alprazolam, bromazepam, chlordiazepoxide, oxazepam, nordazepam, lorazepam
Primarily (Non-selective) Hypnotic Benzodiazepines: nitrazepam, temazepam, flunitrazepam, lormetazepam, triazolam, estazolam, midazolam
Structural Potency of benzodiazepines
There is already a lot of information about equivalent doses of benzodiazepines on a milligram basis. While this is undoubtedly important for clinical practice, it doesn't give the whole story as to why certain benzodiazepines are much more potent than others.
To do this, the therapeutically equivalent doses in milligrams need to be converted to a molar basis and multiplied by their respective bioavailabilities. This tells us exactly how many molecules of a specific benzodiazepine (that reach the circulation) are needed to achieve a standard anxiolytic level. This arbitrary standard in most publications is the level produced by 10 mg of oral diazepam (Valium).
This thought experiment should reveal the common characteristics of the benzodiazepines that bond strongly to the GABA receptor, and thus require the lowest doses on a micromolar basis.
The potency of benzodiazepines in order from most to least (judging from the molecules on a molar basis):
1. Triazolam (Halcion; hypnotic) 1.31 umol
2. Alprazolam (Xanax; anxiolytic) 1.38 umol
3. Clonazepam (Klonopin; anxiolytic, anticonvulsant) 1.43 umol
4. Flunitrazepam (Rohypnol; hypnotic) 1.60 umol
5. Lorazepam (Ativan; anxioltic, anticonvulsant) 2.65 umol
6. Loprazolam (Dormonoct; hypnotic) 2.90 umol
7. Lormetazepam (Noctamid; hypnotic) 3.58 umol
8. Eszopiclone (Lunesta; non-benzodiazepine hypnotic) 4.24 umol
9. Estazolam (ProSom; hypnotic) 4.73 umol
10. Bromazepam (Lexotan; anxiolytic) 14.61 umol
11. Quazepam (Doral; hypnotic) 17.06 umol
12. Zalepion (Sonata; non-benzodiazepine hypnotic) 19.65 umol
13. Zopiclone (Imovane; non-benzodiazepine hypnotic) 21.22 umol
14. Nitrazepam (Mogadon; hypnotic) 30.48 umol
15. Diazepam (Valium; anxiolytic, anticonvulsant, hypnotic) 32.67 umol
16. Medazepam (Nobrium; anxiolytic) 33.23 umol
17. Nordazepam (Nordaz; anxiolytic) 33.25 umol
18. Clorazepate (Tranxene; anxiolytic) 41.27 umol
19. Prazepam (Centrax; anxiolytic) 41.56 umol
20. Flurazepam (Dulmane; hypnotic) 47.08 umol
21. Halazepam (Paxipam; anxiolytic) 51.03 umol
22. Ketazolam (Anxon; anxiolytic) 53.69 umol
23. Clobazam (Frisium; anxiolytic, anticonvulsant) 59.9 umol
24. Zolpidem (Ambien; non-benzodiazepine hypnotic) 59.9 umol
25. Temazepam (Restoril; hypnotic) 63.9 umol
26. Oxazepam (Serax; anxiolytic) 67 umol
27. Chlordiazepoxide (Librium; anxiolytic, anticonvulsant) 75 umol
Please note that the potency of a benzodiazepine has no correlation with euphoria. For example, among drug abusers, Temazepam is and has always been known as a euphoric benzodiazepine and in fact has been banned in many countries due to its recreational abuse, yet its one of the least potent benzodiazepines.
The benzodiazepine equivalency table is firmly based on clinical experience during switch-over to diazepam at start of withdrawal programs. The following dosages are equivalent to 10mg of Diazepam (oral) rather than each other because not all benzodiazepines have the same properties. This is the most updated and accurate equivalency table:
Alprazolam: 0.5mg
Bromazepam: 5.5mg
Chlordiazepoxide: 25mg
Clobazam: 20mg
Clonazepam: 0.5mg
Clorazepate: 15mg
Diazepam: 10mg
Estazolam: 1.5mg
Flunitrazepam: 1mg
Flurazepam: 22mg
Halazepam: 20mg
Ketazolam: 22mg
Loprazolam: 1.5mg
Lorazepam: 1mg
Lormetazepam: 1.5mg
Medazepam: 10mg
Midazolam (PO): 4.76mg
Nitrazepam: 10mg
Nordazepam: 10mg
Oxazepam: 20mg
Prazepam: 15mg
Quazepam: 20mg
Temazepam: 20mg
Triazolam: 0.5mg
Non-benzodiazepine hypnotics
Zaleplon: 20mg
Zolpidem: 20mg
Zopiclone: 15mg
Eszopiclone 3mg
The Half-life of following benzodiazepines [active metabolite in brackets]
Alprazolam: 6-12 hours
Bromazepam: 10-12 hours
Chlordiazepoxide: 5-30 hours [36-200]
Clobazam: 12-60 hours
Clonazepam: 18-50 hours
Clorazepate: [36-200]
Diazepam: 20-100 hours [36-200]
Estazolam: 10-24 hours
Flunitrazepam: 18-26 hours [36-200]
Flurazepam: [40-250]
Halazepam: [30-100]
Ketazolam: 30-100 hours [36-200]
Loprazolam: 6-12 hours
Lorazepam: 10-20 hours
Lormetazepam: 10-12 hours
Medazepam: [36-200]
Midazolam: 1.5-2.5 hours
Nitrazepam: 15-38 hours
Nordazepam: [36-200]
Oxazepam: 4-15 hours
Prazepam: 10-20 hours [36-200]
Quazepam: 25-100 hours
Temazepam: 8-22 hours
Triazolam: 2 hours
Non-benzodiazepine hypnotics
Zaleplon: 2-3 hours
Zolpidem: 2-3 hours
Zopiclone: 5-6 hours
Eszopiclone 3-4 hours
Some history of benzodiazepines… Chlordiazepoxide was the first benzodiazepine to be synthesized and its discovery was by pure chance. It was synthesized in the mid 1950's from work on a chemical dye, quinazolone-3-oxides. It was discovered by accident when in 1957 tests revealed that the compound had hypnotic, anxiolytic and muscle relaxant effects. Three years later chlordiazepoxide was marketed as a therapeutic benzodiazepine medication under the brand name Librium. In 1963 diazepam hit the market under the brand name Valium, as a "simplified" version of chlordiazepoxide, primarily to counteract anxiety symptoms. The most positive results were observed among alcoholic patients. Sleep-related problems were treated with Nitrazepam (Mogadon), which was introduced in 1965, Temazepam (Restoril), which was introduced in 1969, and Flurazepam (Dalmane), which was introduced in 1973.
The molecular mechanisms of Benzodiazepines are well defined in that they enhance the actions of the inhibitory neurotransmitter GABA by binding to specific recognition sites on GABA-a receptors containing six discrete GABA-a (alpha) subunits, GABA alpha1-6. Of those six receptors, benzodiazepines have no affinity for (a 4) and (a 6). Compounds that bind at these modulator sites by enhancing the inhibitory actions of GABA are classified as agonists, those that decrease the actions of GABA are termed inverse agonists whereas compounds that counteract the effects are called antagonists. Flumazenil is a benzodiazepine antagonist that counteracts overdose.
The benzodiazepines represent a large class of drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties. They are potent anticonvulsants and have life-saving properties in the acute management of status epilepticus. There are over 50 known worldwide. These include the variants of the 1,4-benzodiazepines such as the prototype forms diazepam and nordiazepam (also known as nordazepam or N-desmethyl diazepam). Known 3-hydroxy metabolites, namely temazepam, lorazepam and oxazepam, are also registered as benzodiazepines in their own right. The majority of these drugs are excreted as glucuronide conjugates at the 3-hydroxy. Some drugs are metabolized to nordiazepam. These include chlordiazepoxide and clorazepate. 7-Nitro substituted 1,4-benzodiazepines such as
flunitrazepam, nitrazepam, and clonazepam represent a sub-group of drugs that are often abused. These 7-nitro substituted drugs are metabolized by nitroreduction and have no active metabolites. The triazolo ring type benzodiazepines are frequently very potent
and require much lower doses than the older analogs. Some examples include alprazolam, estazolam, and triazolam.
The five various benzodiazepine compounds:
2-Keto Compound
*Includes Diazepam, Flurazepam, Chlordiazepoxide
*All have active metabolites (Most commonly desmethyldiazepam)
*Longest active half-lives (Accumulates from repeated use. Anywhere from 20-200 hours)
3-hydroxy Compound
*Includes Lorazepam, Temazepam, Oxazepam
*No active metabolites
*Intermediate half-lives (generally 8-20 hours)
Triazolo
*Includes Alprazolam, Triazolam, Estazolam
*Few metabolites
*Very short half-lives (anywhere from 3-18 hours)
Imidazo
*Includes Midazolam, Loprazolam and antagonist Flumazenil
*Very potent water-soluble amnesiac sedatives with exception of Flumazenil which is an antagonist, used for overdose in intravenous formulation.
*Short to ultra short half-lives (7 hours or less; Flumazenil roughly 15-30 minutes)
7-Nitro Compound
*Includes Clonazepam, Nitrazepam, Flunitrazepam
*No active metabolites. Metabolized by nitroreduction
*Long half-lives (18-50 hours)
The binding properties and action of benzodiazepines depend on the alpha-subunit profile of the hetero-pentameric receptors: whereas the alpha1 subunit is associated with benzodiazepine type I (BZD1) pharmacology and reportedly mediates sedative as well as amnesic actions of benzodiazepines, the alpha2 subunit confers benzodiazepine type II (BZD2) pharmacology and mediates the anxiolytic actions of benzodiazepines.
All benzodiazepine agonists exert five primary effects and they are:
1. Hypnotic
(Prescribed for: short-term management of insomnia)
2. Anxiolytic
(Prescribed for: treatment of anxiety disorders and phobias; prevention of panic attacks)
3. Anti-convulsant/anti-seizure
(Prescribed for: seizure control; management of status epileptics; prevention of panic attacks)
4. Antispasmodic (Muscle relaxant)
(Prescribed for: treatment of muscle spasms, for example, Tetanus or spastic disorders and Restless legs syndrome.
5. Amnesic
Used as sedatives for patients receiving mechanical ventilation, or those in extreme distress or severe pain. Midazolam is the most common and effective for sleep-induced procedures.
Different benzodiazepines exhibit these primary effects to varying degrees. For example, diazepam (Valium) is a relatively powerful hypnotic, whereas the more modern benzodiazepines such as alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin) are less powerful hypnotics, but are very powerful anxiolytics. Do not assume that because one benzodiazepine makes you sleepier than another that this benzodiazepine is more potent than those that don’t produce sleepiness to the same degree. Often, the reverse is true.
The pharmacological spectrum of benzodiazepine site ligands, ranging from the therapeutic benefits of hypnosis, anxiolysis, anticonvulsant, and muscle relaxation to the potentially unwanted aspects of impaired motor co-ordination, attention and memory, tolerance and dependence and potentiation of the effects of alcohol, are believed to result from interactions with multiple GABA-A receptor “subunits”.
There are six GABA-a subunits, GABA(a 1), GABA(a 2), GABA(a 3), GABA(a 4), GABA(a 5) and GABA(a 6). Of those six receptors, benzodiazepines have no affinity for (a 4) and (a 6). Most effective anti-anxiety benzodiazepines have affinity to both alpha1 and alpha2 subunits while the more effective hypnotics have higher affinity to just the alpha1 subunit
GABA-A receptor subtype containing:
Alpha1: sedation, amnesiac, alcohol interaction, tolerance
Alpha2: anxiolysis, muscle relaxation
Alpha3: anxiolysis, muscle relaxation, sedation
Alpha5: memory, tolerance
The classical benzodiazepine show no selectivity between these GABA-A receptor subtypes and can exhibit the entire spectrum of pharmacological effects, depending on the dose. The “non-benzodiazepines” (zolpidem and zaleplon) show selectivity towards alpha1-containing GABA-A receptors, and these produce a predominant hypnotic pharmacological profile.
The alpha1-containing has been proposed to be responsible for the sedative action; the alpha2 and/or the alpha3 subtypes have been suggested to mediate the anxiolytic activity and the myorelaxation effects, and the alpha5 subtype has been associated with cognition processes.
The anticonvulsant properties of benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.
Primarily Anxiolytic Benzodiazepines: diazepam, clonazepam, alprazolam, bromazepam, chlordiazepoxide, oxazepam, nordazepam, lorazepam
Primarily (Non-selective) Hypnotic Benzodiazepines: nitrazepam, temazepam, flunitrazepam, lormetazepam, triazolam, estazolam, midazolam
Structural Potency of benzodiazepines
There is already a lot of information about equivalent doses of benzodiazepines on a milligram basis. While this is undoubtedly important for clinical practice, it doesn't give the whole story as to why certain benzodiazepines are much more potent than others.
To do this, the therapeutically equivalent doses in milligrams need to be converted to a molar basis and multiplied by their respective bioavailabilities. This tells us exactly how many molecules of a specific benzodiazepine (that reach the circulation) are needed to achieve a standard anxiolytic level. This arbitrary standard in most publications is the level produced by 10 mg of oral diazepam (Valium).
This thought experiment should reveal the common characteristics of the benzodiazepines that bond strongly to the GABA receptor, and thus require the lowest doses on a micromolar basis.
The potency of benzodiazepines in order from most to least (judging from the molecules on a molar basis):
1. Triazolam (Halcion; hypnotic) 1.31 umol
2. Alprazolam (Xanax; anxiolytic) 1.38 umol
3. Clonazepam (Klonopin; anxiolytic, anticonvulsant) 1.43 umol
4. Flunitrazepam (Rohypnol; hypnotic) 1.60 umol
5. Lorazepam (Ativan; anxioltic, anticonvulsant) 2.65 umol
6. Loprazolam (Dormonoct; hypnotic) 2.90 umol
7. Lormetazepam (Noctamid; hypnotic) 3.58 umol
8. Eszopiclone (Lunesta; non-benzodiazepine hypnotic) 4.24 umol
9. Estazolam (ProSom; hypnotic) 4.73 umol
10. Bromazepam (Lexotan; anxiolytic) 14.61 umol
11. Quazepam (Doral; hypnotic) 17.06 umol
12. Zalepion (Sonata; non-benzodiazepine hypnotic) 19.65 umol
13. Zopiclone (Imovane; non-benzodiazepine hypnotic) 21.22 umol
14. Nitrazepam (Mogadon; hypnotic) 30.48 umol
15. Diazepam (Valium; anxiolytic, anticonvulsant, hypnotic) 32.67 umol
16. Medazepam (Nobrium; anxiolytic) 33.23 umol
17. Nordazepam (Nordaz; anxiolytic) 33.25 umol
18. Clorazepate (Tranxene; anxiolytic) 41.27 umol
19. Prazepam (Centrax; anxiolytic) 41.56 umol
20. Flurazepam (Dulmane; hypnotic) 47.08 umol
21. Halazepam (Paxipam; anxiolytic) 51.03 umol
22. Ketazolam (Anxon; anxiolytic) 53.69 umol
23. Clobazam (Frisium; anxiolytic, anticonvulsant) 59.9 umol
24. Zolpidem (Ambien; non-benzodiazepine hypnotic) 59.9 umol
25. Temazepam (Restoril; hypnotic) 63.9 umol
26. Oxazepam (Serax; anxiolytic) 67 umol
27. Chlordiazepoxide (Librium; anxiolytic, anticonvulsant) 75 umol
Please note that the potency of a benzodiazepine has no correlation with euphoria. For example, among drug abusers, Temazepam is and has always been known as a euphoric benzodiazepine and in fact has been banned in many countries due to its recreational abuse, yet its one of the least potent benzodiazepines.
The benzodiazepine equivalency table is firmly based on clinical experience during switch-over to diazepam at start of withdrawal programs. The following dosages are equivalent to 10mg of Diazepam (oral) rather than each other because not all benzodiazepines have the same properties. This is the most updated and accurate equivalency table:
Alprazolam: 0.5mg
Bromazepam: 5.5mg
Chlordiazepoxide: 25mg
Clobazam: 20mg
Clonazepam: 0.5mg
Clorazepate: 15mg
Diazepam: 10mg
Estazolam: 1.5mg
Flunitrazepam: 1mg
Flurazepam: 22mg
Halazepam: 20mg
Ketazolam: 22mg
Loprazolam: 1.5mg
Lorazepam: 1mg
Lormetazepam: 1.5mg
Medazepam: 10mg
Midazolam (PO): 4.76mg
Nitrazepam: 10mg
Nordazepam: 10mg
Oxazepam: 20mg
Prazepam: 15mg
Quazepam: 20mg
Temazepam: 20mg
Triazolam: 0.5mg
Non-benzodiazepine hypnotics
Zaleplon: 20mg
Zolpidem: 20mg
Zopiclone: 15mg
Eszopiclone 3mg
The Half-life of following benzodiazepines [active metabolite in brackets]
Alprazolam: 6-12 hours
Bromazepam: 10-12 hours
Chlordiazepoxide: 5-30 hours [36-200]
Clobazam: 12-60 hours
Clonazepam: 18-50 hours
Clorazepate: [36-200]
Diazepam: 20-100 hours [36-200]
Estazolam: 10-24 hours
Flunitrazepam: 18-26 hours [36-200]
Flurazepam: [40-250]
Halazepam: [30-100]
Ketazolam: 30-100 hours [36-200]
Loprazolam: 6-12 hours
Lorazepam: 10-20 hours
Lormetazepam: 10-12 hours
Medazepam: [36-200]
Midazolam: 1.5-2.5 hours
Nitrazepam: 15-38 hours
Nordazepam: [36-200]
Oxazepam: 4-15 hours
Prazepam: 10-20 hours [36-200]
Quazepam: 25-100 hours
Temazepam: 8-22 hours
Triazolam: 2 hours
Non-benzodiazepine hypnotics
Zaleplon: 2-3 hours
Zolpidem: 2-3 hours
Zopiclone: 5-6 hours
Eszopiclone 3-4 hours
)
) only have myself to blame though...welll a li'l more crack, a 1mg flurazepam 20omg zolpidem shot some outdoor shitty paraguayan weed then xanax with my energy-downer drink (Gin with diluted Coca Leafs, Buprenorphine Loprazolam and if there's good coke around some of it, Oh...and a special version for the ladies with less gin and less bupe that you add no loprazolam more cocaine and real coca cola on the rocks.....ahhhhh, really reccomend doing those with beefeater gin, and filtering after a month or two or do a pitcher and filter before each use), anyways went on a tangent as usual.
, so yeah it's great but watch ou, seeing my homeboy and now Phreex dying of OD's makes me wonder about over knoweldge and self destructive personalities....I'm an addict and on bupe manteinance for which I thank god! I only smoke pot daily apart from my rxd benzos lyroca bupe and other shite.