Otilonium is an inhibitor of L-type (IC50 = 2.3 μM) and T-type calcium channels (IC50s = 0.8, 1.1, and 0.4 μM for Cav3.1, Cav3.2, and Cav3.3, respectively). It is also an antagonist of muscarinic acetylcholine receptors (mAChRs; IC50s = 0.054, 0.4, 0.222, and 0.156 μM for M1, M2, M4, and M5 muscarinic receptors, respectively) and the platelet activating factor (PAF) receptor (IC50 = 0.0552 μM). Otilonium inhibits the inward calcium current in isolated rat colonic smooth muscle cells (EC50 = 885 nM), an effect that can be blocked by the L-type calcium channel inhibitor nifedipine . It inhibits contractions induced by the muscarinic acetylcholine receptor (mAChR) agonist methacholine in isolated circular muscle of the guinea pig proximal colon (IC50 = 3.7 μM). Otilonium (4 mg/kg) decreases fecal excretion and wet dog shakes and increases the tail withdrawal latency in the tail-flick test in a rat model of opioid withdrawal syndrome induced by morphine and naloxone.
