Drug development in anaesthesia: industrial perspective

Abstract

We consider the main reason for low activity is the perception in industry that there is little need for new drugs in anaesthesia because the needs are well addressed by existing agents. If this is not the case then anaesthesiologists need to be more effective in communicating their requirements.

Propofol as a transformative drug in anesthesia: insights from key early investigators

“…by allowing more-frequent use of outpatient surgery) that were not fully envisioned before the drug was available. Although some have argued that there is little clinical need for new anesthetic agents today [13], the case study of propofol suggests that novel drugs have the potential to change and improve clinical practice and in ways that cannot be predicted at the outset. That a new drug might meet as yet unappreciated clinical needs provides a strong motivation for innovation and investment in novel pharmacologic agents in the field.…”

“…Lack of originality in drug development in the field led one expert to wonder why anesthesiologists have moved away from the model of innovative 'clinical pharmacologists' [12]. Two pharmaceutical-industry-based scientists reviewing the state of R&D concluded 'there is little need for new drugs in anesthesia because the needs of anesthesiologists are well covered with existing agents' [13].…”

Retrometabolism‐Based Drug Design and Targeting

“…A number of them maintained high binding affinity at the benzodiazepine receptor (<50 nM), showed good (>100-fold) separation of activity between the (active) ester and the (inactive) acid, and were able to cause loss of the righting reflex (LRR) in rats, an effect associated with benzodiazepine full agonism. Structures such as CNS 7259X (164) [367,369] and CNS 7056 (166) [368,370] (Fig. 37) were selected for development, which has been taken over by CeNeS and later PAION.…”

“…Anaphylactic reactions caused it to be withdrawn, but it is possible that these reactions were in fact caused by the Cremophor solubilizing agent, a polyethoxylated castor oil, used in its formulation. AZD3043 (169), which is being developed by AstraZeneca (originally, TD-4756/THRX-918661 by Theravance), also seems to be a soft anesthetic [369] that is a GABA A allosteric modulator. Its structure has not been officially disclosed yet, but has been suggested [372] to be a close propanidid analog.…”

Is Anesthesiology Going Soft?

“…1 The "soft drug" approach, a strategy wherein novel active compounds are specifically designed to be vulnerable to rapid biotransformation into inactive metabolites, can be employed to develop drugs that meet the unique demands of anesthesia practice. 2 In essence, a soft drug is metabolically fragile and thus rapidly eliminated, 3,4 enabling anesthesiologists to manipulate the drug concentration up and down as needed.…”