Brorphine

Brorphine is a piperidine-based opioid analgesic compound. Some of its structural analogs, originally described in 2018, are functionally biased μ-opioid receptor agonists, showing reduced side effects, especially lacking respiratory depression, when administered in high doses in mice. Importantly, however, this brominated member of the series, while it is a potent μ-opioid agonist, lacks the safety margin seen for several other analogs and shows only limited functional bias, with an EC50 of 4.8nM for GTPγS binding and 182nM for β-arrestin recruitment. Brorphine can instead be regarded as a typical opioid agonist, based upon its performance under various assay conditions, including robust arrestin recruitment. Brorphine is therefore not preferable, from a safety perspective, to common street opioids. Moreover, its safety profile in any animal model has never been established. In addition to respiratory risks, it is expected to be cardiotoxic because it is a potent hERG potassium ion channel inhibitor, a mechanism that can prompt deadly cardiac arrhythmias, similar to dextropropoxyphene, a previously approved opioid medication which was withdrawn from sale because of this side effect. Despite the potential safety issues and lack of animal studies, it has been sold as a designer drug since mid-2019, initially being identified in the US Midwest, though it has since been found in 2020 in Belgium. Given its potency, lack of functional bias, and hERG inhibition, it can be expected to be a comparatively toxic opioid, and indeed multiple deaths from its abuse have been reported. It is related in chemical structure to compounds such as benzylfentanyl and bezitramide, though it is sufficiently structurally distinct to fall outside the formal definition of a


Brorphine is a piperidine-based opioid analgesic compound. Some of its structural analogs, originally described in 2018, are functionally biased μ-opioid receptor agonists, showing reduced side effects, especially lacking respiratory depression, when administered in high doses in mice. Importantly, however, this brominated member of the series, while it is a potent μ-opioid agonist, lacks the safety margin seen for several other analogs and shows only limited functional bias, with an EC50 of 4.8nM for GTPγS binding and 182nM for β-arrestin recruitment. Brorphine can instead be regarded as a typical opioid agonist, based upon its performance under various assay conditions, including robust arrestin recruitment. Brorphine is therefore not preferable, from a safety perspective, to common street opioids. Moreover, its safety profile in any animal model has never been established. In addition to respiratory risks, it is expected to be cardiotoxic because it is a potent hERG potassium ion channel inhibitor, a mechanism that can prompt deadly cardiac arrhythmias, similar to dextropropoxyphene, a previously approved opioid medication which was withdrawn from sale because of this side effect. Despite the potential safety issues and lack of animal studies, it has been sold as a designer drug since mid-2019, initially being identified in the US Midwest, though it has since been found in 2020 in Belgium. Given its potency, lack of functional bias, and hERG inhibition, it can be expected to be a comparatively toxic opioid, and indeed multiple deaths from its abuse have been reported. It is related in chemical structure to compounds such as benzylfentanyl and bezitramide, though it is sufficiently structurally distinct to fall outside the formal definition of a "fentanyl analogue" in jurisdictions such as the US and New Zealand which have Markush structure controls over this family of drugs.
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