Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent.

A program to identify novel intravenous sedatives with a short and predictable duration of action was initiated in the late 1990's by Glaxo Wellcome. The program focussed on the identification of ester-based benzodiazepine derivatives that are rapidly broken down by esterases. Remimazolam was identified as one of the lead compounds.

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination.

A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.

Background: A new benzodiazepine, remimazolam, which is rapidly metabolized by tissue esterases to an inactive metabolite, has been developed to permit a fast onset, a short, predictable duration of sedative action, and a more rapid recovery profile than currently available drugs. We report on modeling of the data and simulations of dosage regimens for future study.

Methods: A phase I, single-center, double-blind, placebo and active controlled, randomized, single-dose escalation study was conducted.

A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics.

Background: A new benzodiazepine, remimazolam, metabolized by tissue esterases to an inactive compound, CNS 7054, has been developed to permit a fast onset, a short and more predictable duration of sedative action, and a more rapid recovery profile than with currently available benzodiazepines. We report on the safety and efficacy of the first human study.

Methods: A phase I, single-center, double-blind, placebo- and active-controlled, randomized, single-dose escalation study was conducted.

CNS 7056: a novel ultra-short-acting Benzodiazepine.

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile.

Drug development in anaesthesia: industrial perspective.

Purpose Of Review: In this review, we summarize the new drugs in development in the anaesthesia field.

Recent Findings: There are some interesting approaches, including pro-drugs of propofol such as Aquavan (MGI Pharma, Bloomington, Minnesota, USA) and novel 'soft-drug' sedatives and hypnotics (e.g.

Morphine-6-glucuronide: actions and mechanisms.

Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the micro-opioid receptor.

Memantine. Merz.

Memantine hydrochloride, an NMDA antagonist, was launched in Germany by Merz in 1989 for the treatment of dementia, an indication for which development was continuing in other markets. It is also under development by Merz, Lundbeck, Neurobiological Technologies Inc (NTI) Forest Laboratories and Suntory for the potential treatment of Alzheimer's disease (AD), AIDS-related dementia and pain in patients with neuropathy, and by Allergan for the potential treatment of ocular disease. By July 2001, a regulatory filing for neuropathic pain was expected in 2003.