Synthesis and smooth muscle-selective relaxant activity of a piperidine analogue: 1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride.
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.
Federal Urdu University of Arts, Science and Technology, University Road, Karachi, Pakistan.
Syed Intasar Hussain
SI
Taqvi
Muhammad Nabeel
MN
Ghayur
Anwarul Hassan
AH
Gilani
Zafar Saeed
ZS
Saify
Mohammad Tariq
MT
Aftab
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects; D008139:Loperamide / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
C509024:1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride; D000930:Antidiarrheals; D010276:Parasympatholytics; D010880:Piperidines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D008139:Loperamide; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine