fadolmidine (MPV-2426) / Recro Pharma, Orion Corp - LARVOL DELTA

Modulation of spinal morphine pharmacokinetics and antinociception by α2-adrenergic agonists in the male rat. (PubMed, Neuropharmacology) - "Subcutaneous dexmedetomidine effectively targeted lumbar morphine towards the injection site resulting in a 3335-fold (95% CI: 929-11978) lower brain-to-injection site ratio, versus a 355-fold (95% CI: 196-641) difference with saline. By improving spinal opioid targeting, α2-adrenergic agonists dexmedetomidine and fadolmidine may reduce supraspinal side effects, enabling safe and efficacious intrathecal analgesia."

Journal • PK/PD data • Preclinical • Anesthesia

Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation. (PubMed, J Sex Med) - "The observation that drugs acting at central but not peripheral α-adrenoceptors prolong ejaculation latency without affecting any other parameter of sexual behavior or sexual incentive motivation suggests that this kind of drug may be suitable for treating premature ejaculation. Jyrki L., Elisa V.-A., Xi C., et al. Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation. J Sex Med 2021;XX:XXX-XXX."

Journal • Preclinical • Anesthesia • Sexual Disorders

Effects of fadolmidine, an α -adrenoceptor agonist, as an adjuvant to spinal bupivacaine on antinociception and motor function in rats and dogs. (PubMed, Pharmacol Res Perspect) - "α -Adrenoceptor agonists such as clonidine and dexmedetomidine are used as adjuvants to local anesthetics in regional anesthesia. Taken together, these studies show that fadolmidine as an adjuvant to intrathecal bupivacaine provides enhanced sensory-motor block and enables a reduction of the doses of both drugs. The results indicate that co-administration of fadolmidine with intrathecal bupivacaine was able to achieve an enhanced antinociceptive effect without hypotension and could thus represent a suitable combination for spinal anesthesia."

Journal • Preclinical • Anesthesia • Hypotension • Pain

Fadolmidine - Favourable adverse effects profile for spinal analgesia suggested by in vitro and in vivo models. (PubMed, Eur J Pharmacol) - "In resting conditions, fadolmidine decreased HR dose-dependently and increased initial MAP, whereas in actively moving rats, there were no effects at analgesic doses. The results suggest that at anticipated analgesic clinical doses, IT fadolmidine provides analgesia without significant adverse effects on sedation, MAP or HR and with only modest effects on kidney function and urodynamics."

Adverse events • Journal • Preclinical • Anesthesia • Cardiovascular • Pain

Pharmacodynamics of intrathecal and epidural fadolmidine, an α-adrenoceptor agonist, after bolus and infusion in dogs-comparison with clonidine. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "At analgesic doses, fadolmidine injection induced moderate initial hypertension concomitantly with a decrease in heart rate whereas clonidine evoked hypotension and bradycardia. These results suggest that especially when non-opioid long-term pain relief is needed, an intrathecal infusion of fadolmidine can provide long-term antinociception with less of the known use-limiting adverse effects associated with clonidine."

Journal • PK/PD data