Fadolmidine, formerly known as MPV-2426, is a novel and highly potent alpha2 -adrenoceptor (alpha2) -AR) agonist developed for spinal analgesia. Fadolmidine displayed high affinity and full agonist efficacy at all three human alpha2-adrenoceptor subtypes (A, B and C) in transfected CHO cells with EC50 (nM) of 0.4, 4.9 and 0.5, respectively. Fadolmidine inhibited also electrically evoked contractions in rat vas deferens demonstrating the activation of rodent presynaptic alpha2D-adrenoceptors with an EC50 of 6.4 nM. Moreover, fadolmidine was a full agonist at human alpha1A-adrenoreceptor (EC50 22 nM) and alpha1B-adrenoreceptor (EC50 3.4 nM) in human LNCaP cells and transfected HEK cells, respectively. Agonism at the alpha1-adrenoceptor was also observed in rat vas deferens preparations although at lower potency (EC50 5.6 microM). Fadolmidine demonstrated potent alpha2-adrenoceptor agonist activity also in vivo by inhibiting electrically induced tachycardia in pithed rats and increasing mean arterial pressure in anaesthetised rats. However, after systemic administration, fadolmidine had considerably weaker CNS-mediated effects (mydriasis and sedation) compared to dexmedetomidine possibly due to limited penetration through the blood brain barrier by fadolmidine . In a conclusion, fadolmidine is a potent full agonist at all three alpha2-adrenoceptor subtypes with a pharmacological profile compatible with a therapeutic value e.g. after spinal administration. (Eur J Pharmacol. 2008 Dec 3;599(1-3):65-71.) References: Berg T. Angiotensin AT1 - α2C-Adrenoceptor Interaction Disturbs α2A-auto-Inhibition of Catecholamine Release in Hypertensive Rats. Front Neurol. 2013 Jun 10;4:70. doi: 10.3389/fneur.2013.00070. PubMed PMID: 23772221; PubMed Central PMCID: PMC3677154.

纯度：≥98%

CAS：189353-32-0