Benzodiazepines midazolam

Mice lacking the 8 subunit, which is mainly expressed in cerebellum and thalamus, display an attenuation of ssatrighting reflex time following the administration of the neurosteroids, alphaxalone and pregnanolone, while the responses to propofol, etomindate, ketamine and the benzodiazepine midazolam were unaffected. This demonstrates the role of GABAa receptors containing the 8 subunit for neurosteroid action. 

McGregor, I. S., Hargreaves, G. A., Apfelbach, R. and Hunt, G.E. (2004) Neural correlates of cat odor-induced anxiety in rats region-specific effects of the benzodiazepine midazolam. J. Neurosci. 24, 4134-44. 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Although these experiments analyzed the hypothesis that convulsant activity is required for the antidepressant-like effects of ( + )BW373U86, it did not thoroughly address the question of whether seizure activity is required for the antidepressant-like effects of delta opioid agonists. The benzodiazepine midazolam was demonstrated to inhibit seizure activity [49,50] however, seizure activity was not directly measured in the study by Broom et al. [35]. Interestingly, limited work has been done with the seizure activity of delta opioid agonists. One study demonstrated that the delta opioid agonist... 

General anesthetics are rarely given alone. In addition to the analgesic agents just mentioned, benzodiazepines (midazolam, Versed diazepam, Valium ) are commonly used as adjuncts for the relief of anxiety, amnesia, and sedation prior to induction of anesthesia. Neuromuscular blockers (e.g., succinylcholine or pancuronium) can also be administered during the induction of anesthesia to relax skeletal muscles. 

Muscle rigidity after high-dose opioids can be reduced by the benzodiazepines midazolam and diazepam (SEDA-19, 82). 

These findings for opiates are in contrast to findings with the barbiturate thiopental and the benzodiazepines midazolam and triazolam (14, 25, 26). 

Annelating the 1,2-bond of ring B with an additionai eiectron-rich (i.e., proton acceptor) ring, such as s-triazoie or imidazole, also results in pharmacologically active benzodiazepine derivatives with high affinity for the BZR (Fig. 22.17). For example, the s-triazolo-benzodiazepines triazolam, alprazolam, and estazolam and the imidazo-benzodiazepine midazolam are popularly prescribed, clinically effective anxiolytic agents (Fig. 22.16). 

Recently, Jahnsen and Laursen (1981) have shown that both the hyperpolarizing and depolarizing action of GABA on the CAl pyramidal cells of the hippocampal slice are enhanced by the addition of the water-soluble benzodiazepine, midazolam (10 M), to the perfusion fluid. 

Benzodiazepines midazolam is also metabolized by the isoenzyme CYP3 A4, which when inhibited by high-dose aprepitant will lead to an increase in plasma levels for any given dose. 

---