title: α-Adrenoceptor antagonistic and hypotensive properties of novel arylpiperazine derivatives of pyrrolidin-2-one.
abstract: This study focused on a series of pyrrolidin-2-one derivatives connected via two or four methylene units to arylpiperazine fragment. The compounds obtained for α₁- and α₂-adrenoceptors were assessed. The compound with highest affinity for the α₁-adrenoceptors was 1-{4-[4-(2-chloro-phenyl)-piperazin-1-yl]-butyl}-pyrrolidin-2-one (10 h) with pKi=7.30. Compound with pKi (α₁) ⩾6.44 were evaluated in functional bioassays for intrinsic activity at α₁A- and α₁B-adrenoceptors. All compounds tested were antagonists of the α₁B-adrenoceptors. Additionally, compounds 10e and 10h were α₁A-adrenoceptors antagonist. The dual α₁A-/α₁B-adrenoceptors antagonists, compounds 10e and 10h were also tested in vivo for their hypotensive activity in rats. These compounds, when dosed of 1.0 mg/kg iv in normotensive, anesthetized rats, significantly decreased systolic and diastolic pressure and their hypotensive effects lasted for longer than one hour.
authors: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors: Paula
authors: P
authors: Zaręba
authors: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Magdalena
authors: M
authors: Dudek
authors: Department of Pharmacological Screening, Jagiellonian University, Medical College, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Klaudia
authors: K
authors: Lustyk
authors: Department of Pharmacobiology, Jagiellonian University, Collegium Medicum, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Agata
authors: A
authors: Siwek
authors: Department of Pharmacobiology, Jagiellonian University, Collegium Medicum, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Gabriela
authors: G
authors: Starowicz
authors: Department of Pharmacological Screening, Jagiellonian University, Medical College, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Marek
authors: M
authors: Bednarski
authors: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Leszek
authors: L
authors: Nowiński
authors: Department of Pharmacological Screening, Jagiellonian University, Medical College, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Katarzyna
authors: K
authors: Raźny
authors: Department of Pharmacological Screening, Jagiellonian University, Medical College, 9, Medyczna Street, PL 30-688 Kraków, Poland.
authors: Jacek
authors: J
authors: Sapa
authors: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors: Barbara
authors: B
authors: Malawska
authors: Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: mfkkulig@cyf-kr.edu.pl.
authors: Katarzyna
authors: K
authors: Kulig
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1
keywords: Hypotensive activity; Long-chain arylpiperazines; Pyrrolidin-2-one derivatives; α-Adrenoceptors antagonists