Molecular characterization of off-target activities of telithromycin: a potential role for nicotinic acetylcholine receptors.
Adverse effects have limited the clinical use of telithromycin. Preferential inhibition of the nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (α3β2 and NMJ), the ciliary ganglion of the eye (α3β4 and α7), and the vagus nerve innervating the liver (α7) could account for the exacerbation of myasthenia gravis, the visual disturbance, and the liver failure seen with telithromycin use. The studies presented here enable the prediction of expected side effects of macrolides in development, such as solithromycin (CEM-101).
Bertrand
Daniel
D
HiQScreen, 15 rue de l'Athénée, 1206 Geneva, Switzerland. daniel.bertrand@hiqscreen.com
Bertrand
Sonia
S
Neveu
Estelle
E
Fernandes
Prabhavathi
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048628:Ketolides / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D015394:Molecular Structure; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis
D000900:Anti-Bacterial Agents; D048628:Ketolides; D011978:Receptors, Nicotinic; C106791:telithromycin