Synthesis and smooth muscle-selective relaxant activity of a piperidine analogue: 1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride. 2006

Syed Intasar Hussain Taqvi, and Muhammad Nabeel Ghayur, and Anwarul Hassan Gilani, and Zafar Saeed Saify, and Mohammad Tariq Aftab
Federal Urdu University of Arts, Science and Technology, University Road, Karachi, Pakistan.

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and K+ (75 mM)-induced contractions of isolated rabbit jejunum with respective EC50 values of 0.01 mM (0.01-0.02, 95% Cl) and 0.30 mM (0.17-0.56). The Ca++ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the Ca++ dose-response curves to the right, similar to that produced by verapamil (0.1-1.0 microM), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on K+ (75 mM)-induced contractions with an EC50 value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine (1 microM) control peak responses with EC50 value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated Ca++ channels.

UI MeSH Term Description Entries
D007422 Intestines The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE. Intestine
D007583 Jejunum The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Jejunums
D008139 Loperamide One of the long-acting synthetic ANTIDIARRHEALS; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. Imodium,Loperamide Hydrochloride,Loperamide Monohydrochloride,R-18553,Hydrochloride, Loperamide,Monohydrochloride, Loperamide,R 18553,R18553
D008297 Male Males
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010276 Parasympatholytics Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. Antispasmodic,Antispasmodic Agent,Antispasmodic Drug,Antispasmodics,Parasympathetic-Blocking Agent,Parasympathetic-Blocking Agents,Parasympatholytic,Parasympatholytic Agent,Parasympatholytic Drug,Spasmolytic,Spasmolytics,Antispasmodic Agents,Antispasmodic Drugs,Antispasmodic Effect,Antispasmodic Effects,Parasympatholytic Agents,Parasympatholytic Drugs,Parasympatholytic Effect,Parasympatholytic Effects,Agent, Antispasmodic,Agent, Parasympathetic-Blocking,Agent, Parasympatholytic,Agents, Antispasmodic,Agents, Parasympathetic-Blocking,Agents, Parasympatholytic,Drug, Antispasmodic,Drug, Parasympatholytic,Drugs, Antispasmodic,Drugs, Parasympatholytic,Effect, Antispasmodic,Effect, Parasympatholytic,Effects, Antispasmodic,Effects, Parasympatholytic,Parasympathetic Blocking Agent,Parasympathetic Blocking Agents
D010880 Piperidines A family of hexahydropyridines.

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