26astr00
Greenlighter
- Joined
- Apr 7, 2016
- Messages
- 21
New benzodiazepines are developed every year, this guide should help you figuring out the potency of newly developed benzodiazepines.
Benzodiazepines are used as daytime anxiolytics, sleep inducers, anesthetics, anticonvulsants (also known as antiseizure agents), and muscle relaxants. Examination of the basic pharmacodynamic properties of the benzodiazepines (defined as receptor-specific binding activity) show that the clinically useful benzodiazepines exhibit comparable sedative activity at therapeutically comparable doses. The use of a specific benzodiazepine as a hypnotic is based primarily on pharmacokinetic properties and marketing considerations. Hypnotics are unusual in that they normally are given as a single dose. The following variables will determine how well a benzodiazepine will work as a hypnotic:
1) Is acute tolerance developed to the benzodiazepine that will diminish CNS effects before the drug is eliminated from the CNS,
2) is redistribution of the benzodiazepine from the CNS to other tissues very rapid, and
3) is there a rapid drug elimination by biotransformation and the metabolite active?
Structure-activity relationship
1. A methylgroup (-CH3) on position N1 is the most active. Large substituents are less active. In the body, the -CH3 is demethylmated, forming new active metabolites.
2. A carbonylgroup on C2 is optimal for the activity. Imidazole and triazole derivatives can also bind in the same manner: they have a higher activity but a shorter duration of action.
3. A hydroxylgroup (-OH) on C3 shortens the activity. A carboxylgroup on the other hand will cause a slower metabolisation in the body.
4. A benzene ring on C5 promotes activity.
5. An electronegative group (Cl, Br, NO2) on C7 is crucial for the activity.
6. An elektronegative substitute (Cl, F) on C2' (what is also known as the 'ortho position') leads to a higher activity.
7. Position C6, C8 and C9 should be free of any substituents, otherwise activity is lowered drastically.
What are good alternatives to prescription drugs?
Diclazepam 2 mg (half life 42h)
is a good alternative to Diazepam/Valium 2-10 mg (half life 36-200h)
Structure is almost the same, the only difference being the extra -Cl group on C2'
Pyrazolam 1 mg (half life 17h)
is a good alternative to Alprazolam/Xanax 0.25-2 mg (half life 9-20h)
Structure is almost the same, the only difference being the -Cl group on C7 being replaced by a -Br group
Flubromazepam 8 mg (half life 106h)
is a good alternative to Flunitrazepam/Rohypnol 1 mg (half life 36-200h)
Structure is pretty similar, two differences are apparent: the -NO2 group on C7 is replaced by a -Br group and the methylgroup on N1 has disappeared
Other common benzodiazepines found online are:
- Metizolam 2 mg
- Deschloroetizolam
- Clonazolam*
- Flubromazolan*
- Nifoxipam
- Meclonazepam
*Concerns have been raised that clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines, due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg.
Benzodiazepines are used as daytime anxiolytics, sleep inducers, anesthetics, anticonvulsants (also known as antiseizure agents), and muscle relaxants. Examination of the basic pharmacodynamic properties of the benzodiazepines (defined as receptor-specific binding activity) show that the clinically useful benzodiazepines exhibit comparable sedative activity at therapeutically comparable doses. The use of a specific benzodiazepine as a hypnotic is based primarily on pharmacokinetic properties and marketing considerations. Hypnotics are unusual in that they normally are given as a single dose. The following variables will determine how well a benzodiazepine will work as a hypnotic:
1) Is acute tolerance developed to the benzodiazepine that will diminish CNS effects before the drug is eliminated from the CNS,
2) is redistribution of the benzodiazepine from the CNS to other tissues very rapid, and
3) is there a rapid drug elimination by biotransformation and the metabolite active?
Structure-activity relationship
1. A methylgroup (-CH3) on position N1 is the most active. Large substituents are less active. In the body, the -CH3 is demethylmated, forming new active metabolites.
2. A carbonylgroup on C2 is optimal for the activity. Imidazole and triazole derivatives can also bind in the same manner: they have a higher activity but a shorter duration of action.
3. A hydroxylgroup (-OH) on C3 shortens the activity. A carboxylgroup on the other hand will cause a slower metabolisation in the body.
4. A benzene ring on C5 promotes activity.
5. An electronegative group (Cl, Br, NO2) on C7 is crucial for the activity.
6. An elektronegative substitute (Cl, F) on C2' (what is also known as the 'ortho position') leads to a higher activity.
7. Position C6, C8 and C9 should be free of any substituents, otherwise activity is lowered drastically.
What are good alternatives to prescription drugs?
Diclazepam 2 mg (half life 42h)
is a good alternative to Diazepam/Valium 2-10 mg (half life 36-200h)
Structure is almost the same, the only difference being the extra -Cl group on C2'
Pyrazolam 1 mg (half life 17h)
is a good alternative to Alprazolam/Xanax 0.25-2 mg (half life 9-20h)
Structure is almost the same, the only difference being the -Cl group on C7 being replaced by a -Br group
Flubromazepam 8 mg (half life 106h)
is a good alternative to Flunitrazepam/Rohypnol 1 mg (half life 36-200h)
Structure is pretty similar, two differences are apparent: the -NO2 group on C7 is replaced by a -Br group and the methylgroup on N1 has disappeared
Other common benzodiazepines found online are:
- Metizolam 2 mg
- Deschloroetizolam
- Clonazolam*
- Flubromazolan*
- Nifoxipam
- Meclonazepam
*Concerns have been raised that clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines, due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg.
