Adrenergic Modulation With Photochromic Ligands

Abstract

Adrenoceptors are ubiquitous and regulate heart and respiratory rate, digestion, metabolism, and vascular tone. They can be activated or blocked with adrenergic drugs, but systemic administration causes broad adverse effects. We have developed photochromic ligands (adrenoswitches) to switch on and off adrenoceptor activity on demand at selected locations. Their pharmacology, photochromism, bioavailability and lack of toxicity allow photomodulating adrenergic signalling, as demonstrated by controlling locomotion in zebrafish and pupillary responses in blind mice. File list (2) download file view on ChemRxiv Adrenergic modulation with photochromic ligands (main ... (573.43 KiB) download file view on ChemRxiv Adrenergic modulation with photochromic ligands (SI).pdf (2.41 MiB)

Photoswitchable Serotonins for Optical Control of the 5‐HT2A Receptor**

“…As an alternative to classical pharmacology, photopharmacology has emerged as a means of gaining further precision through the development of photosensitive compounds whose activity can be modified depending on the wavelength of illumination. [8][9][10] Photopharmacological compounds have enabled the optical control of a variety of GPCRs, including family A (μ-opioid receptor, [11] dopamine receptors, [12,13] histamine receptors, [14] adenosine receptors, [15] muscarinic receptors, [16] adrenergic receptors, [17] fatty acid receptors, [18] lysophospholipid receptors, [19,20] and cannabinoid receptors [21,22] ), family B (glucagon-like peptide 1 receptor [23,24] ), and family C GPCRs (metabotropic glutamate receptors [25][26][27][28] ). For further precision, including the ability to target the effects of light to genetically-defined cell populations, photoswitches may be covalently tethered to a genetically engineered labeling domain (i.e.…”

Photoswitchable Serotonins for Optical Control of the 5‐HT2A Receptor**

“…As an alternative to classical pharmacology, photopharmacology has emerged as a means of gaining further precision through the development of photosensitive compounds whose activity can be modified depending on the wavelength of illumination. [8][9][10] Photopharmacological compounds have enabled the optical control of a variety of GPCRs, including family A (μ-opioid receptor, [11] dopamine receptors, [12,13] histamine receptors, [14] adenosine receptors, [15] muscarinic receptors, [16] adrenergic receptors, [17] fatty acid receptors, [18] lysophospholipid receptors, [19,20] and cannabinoid receptors [21,22] ), family B (glucagon-like peptide 1 receptor [23,24] ), and family C GPCRs (metabotropic glutamate receptors [25][26][27][28] ). For further precision, including the ability to target the effects of light to genetically-defined cell populations, photoswitches may be covalently tethered to a genetically engineered labeling domain (i.e.…”

Photoswitchable Serotonins for Optical Control of the 5-HT2A Receptor

“…As an alternative to classical pharmacology, photopharmacology has emerged as a means of gaining further precision through the development of photosensitive compounds whose activity can be modified depending on the wavelength of illumination [8][9][10] . Photopharmacological compounds have enabled the optical control of a variety of GPCRs, including class A (µ-opioid receptor, 11 dopamine receptors, 12,13 histamine receptors, 14 adenosine receptors, 15 muscarinic receptors, 16 adrenergic receptors 17 , fatty acid receptors, 18 lysophospholipid receptors, 19,20 and cannabinoid receptors 21,22 ), class B (glucagon-like peptide 1 receptor 23,24 ), and class C GPCRs (metabotropic glutamate receptors [25][26][27][28] ). For further precision, including the ability to target the effects of light to genetically-defined cell populations, photopharmaceuticals may be covalently tethered to a genetically engineered receptor containing a labeling domain (i.e.…”