Diazepam structure activity relationship
structure-activity relationship within this class will be mentioned so as to place this novel and benzodiazepines of classical type 2, diazepam, nordazepam or . Azathioprine structure activity relationship of diazepam. Synthesis and +91,+ Midazolam, diazepam and flumazenil are Effects; receptors, gaba-a/metabolism; . Midazolam, diazepam and flumazenil are metabolized by cytochrome P (CYP ) effects; Receptors, GABA-A/metabolism; Structure-Activity Relationship.
Midazolam for injection is supplied as the hydrochloride salt and the pH of the solution is adjusted to 3. After injection into the blood typical pH 7. Regarding midazolam and use as part of subarachnoid or epidural blocks, and related to an IV Anaesthetics MCQ in Febmidazolam is not active at mu receptors, but may be active at delta and kappa receptors as an agonist.
Structural activity relationships of benzodiazepines
Its major uses in anaesthetic and intensive care practice are: Midazolam is a imidazobenzodiazepine which has a pH-dependent structure. Major side-effects include hypotension, apnoea, airway obstruction and loss of protective airwary reflexes.
Midazolam is the only clinically available water-soluble benzodiazepine and is commonly used as intravenous sedative or anaesthetic. The water solubility of this imidazobenzodiazepine is dependent on a pH-dependent change in structure. It is not much used for induction of general anaesthesia because of its slow onset and slow offset compared to alternatives eg thiopentone, propofol.
Its advantage over these alternatives is cardiorespiratory stability. In an in vitro functional assay, midazolam is a weak agonist at the delta-opioid receptor, whereas all three benzodiazepines are kappa-opioid agonists.
These findings may partially explain the mechanism of benzodiazepine-induced spinal analgesia. Our results show that large concentrations of midazolam, chlordiazepoxideand diazepam displace the binding of -diprenorphine-an opiate radioligand from kappa receptors.
They also induce sleep and increase overall sleep quality. All these actions of benzodiazepines can be attributed to their structure with little change in few drugs. We will see here how a small structural change can affect the pharmacodynamic and pharmacokinetic properties of these drugs. Why SAR is important?
Studying of structural activity relationships SAR is very important to develop drugs with more selectivity to the target or more potent or more active.
- Structure activity relationship of diazepam and midazolam
- SAR of BENZODIAZEPINES authorSTREAM
Sometimes, SAR can also be used to improve duration of action and bioavailability. It can be used to prepare a series of drugs with common structural features prove to have significant activity. Structural activity relationships The common structural feature of benzodiazepines involves six plus seven numbered fused ring system with two nitrogens. Numbering is started from adjacent nitrogen to the bridge heads and second nitrogen is given 4th position.
Structure activity relationship of diazepam and midazolam
For more details, see nomenclature of benzodiazepines. At 1st position, a small alkyl group is optimal for activity.
For example, diazepam and temazepam has methyl group at 1st position. For example, benzodiazepines like oxazepam, lorazepam and nitrazepam simply have hydrogen at 1st position.
A carbonyl group at 2nd position is essential for activity You can easily observe this group in many of the benzodiazepines such as diazepam, oxazepm etc. Here we can found two exceptions. First is at chlordiazepoxide and second at fused benzodiazepines. Fused benzodiazepines like alprazolam, midazolam and triazolam interact with GABA receptors through triazole or imidazole ring.
All other benzodiazepines require a keto group at 2nd position. But in-vivo it can undergo oxidative deamination to produce demoxepam with keto group at second position.
This again proved that keto group at 2nd position is essential for activity. It is obvious that drugs or metabolites which are highly polar can undergo direct conjugation and hence directly excreted.
A polar functional group at 3rd position increases excretion thereby decrease duration of action. Drugs like lorazepm, oxazepam and temazepam have hydroxyl group at 3rd position making all these drugs polar and easily excretable. Hence all these drugs have short duration of action.Structure Activity Relationship of Benzodiazepines (BZDs)
Oxazepam and lorazepam are highly polar and can be excreted without phase I metabolism. Temazepam also shows a little phase I reaction.
Midazolam and other benzodiazepines.
It undergoes demethylation and converted into oxazepam and then excreted. This is essential for activity and saturation of this double bond may decrease the activity.
Even shift of the double bond to 3rd and 4ht position decreases the activity.