title: Safety, Tolerability, and Antihypertensive Effect of SER100, an Opiate Receptor-Like 1 (ORL-1) Partial Agonist, in Patients With Isolated Systolic Hypertension.
abstract: The purpose of the present trial was to evaluate safety, tolerability, and effect on systolic blood pressure (SBP) of SER100 in a small group of patients with isolated systolic hypertension (ISH) in treatment with at least 1 antihypertensive drug. Eligible patients were randomized to either SER100 (10 mg) or placebo in a crossover design, and 2 doses were given subcutaneously (SC), 8 hours apart, on 2 consecutive days. On all treatment days patients were monitored with an ambulatory blood pressure measurement device for 12 daytime hours. Seventeen patients completed treatment. There were no serious or severe adverse events. Relative to placebo SER100 induced an average reduction of SBP during the 2 treatment days of 7.0 mm Hg (P = 0.0032), whereas the average reduction of diastolic blood pressure (DBP) over the same period was 3.8 mm Hg (P = 0.0011). For patients with ISH, this short-term cross-over study of SC SER100 demonstrated an acceptable safety profile and consistent, significant lowering of SBP and DBP. As initial clinical proof of concept for a new class of drugs, a nociceptin agonist peptide, the results were encouraging and warrant further research.
authors.affiliation: Division of Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kantola
authors.affiliation: CRST Ltd, Itäinen Pitkäkatu, Turku, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.affiliation: Serodus ASA, Gaustadalleen, Oslo, Norway.
authors.forename: Trygve
authors.initials: T
authors.lastname: Gulbrandsen
authors.affiliation: Smerud Medical Research International AS, Karenslyst alle, Oslo, Norway.
authors.forename: Nils
authors.initials: N
authors.lastname: Meland
authors.affiliation: Smerud Medical Research International AS, Karenslyst alle, Oslo, Norway.
authors.forename: Knut T
authors.initials: KT
authors.lastname: Smerud
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists; D000094942:Nociceptin Receptor
chemical_list: D000959:Antihypertensive Agents; D009842:Oligopeptides; D011957:Receptors, Opioid; C473470:ZP120; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human
keywords: NOP partial agonist; OP4; ORL-1 agonist; SER100; crossover; isolated systolic hypertension; placebo-controlled randomized clinical trial