title: Current statins show calcium channel blocking activity through voltage gated channels.
abstract: Statins are used for treatment of hypercholestremia. Common adverse reports associated with use of statins are generalized bodyache, rhabdomyolysis, muscles weakness and gastrointestinal disorders. The current work is an attempt to explain how smooth muscles of gastrointestinal tissues are affected by the current statins (Simvastatin, atorvastatin, fluvastatin and rosuvastatin).
  
  
  
  Effects of the current statins were studied on spontaneous activity of isolated rabbits' jejunal preparations. Different molar concentrations (10(-12)-10(-2)M) of the statins were applied on spontaneously contracting rabbits' jejunal preparations. As statins relaxed spontaneous activity, so we tested the statins on KCl (80 mM) induced contractions in similar test concentrations. Positive relaxant statins were tested again through construction of Calcium Concentration Response Curves (CCRCs) in the absence and presence of the statins using verapamil, a standard calcium channel blocker. CCRCs of statins were compared with CCRCs of verapamil.
  
  
  
  Simvastatin, atorvastatin, fluvastatin and rosuvastatin relaxed the spontaneous and KCl-induced contractions. IC50 for simvastatin on spontaneous rabbit's jejunal preparations is -5.08 ± 0.1 Log 10 M. Similarly, IC50 for KCl-induced contractions is -4.25 ± 0.01 Log 10 M. Mean IC50 (Log 10 M) for atorvastatin on spontaneous rabbit's jejunal preparations and KCl-induced contractions are -5.19 ± 0.07 and -4.37 ± 0.09, respectively. Fluvastatin relaxed spontaneous activity of rabbits' jejunal preparations with an IC50 (Log 10 M) -4.5 ± 0.03. Rosuvastatin relaxed spontaneous as well as KCl (80 mM) induced contractions with respective IC50 (Log 10 M) -3.62 ± 0.04 and -4.57 ± 0.06. In case of CCRCs, tissues pre-treated with 4.6 μg/ml of simvastatin, have IC50 = -1.84 ± 0.03 [log (Ca(++)) M] vs control IC50 = -2.54 ± 0.04 [log (Ca(++)) M]. Similarly, atorvastatin, fluvastatin and rosuvastatin produced significant right shift in IC50 for CCRCs (P ≤ 0.05). In case of verapamil, IC50 for control curves is -2.45 ± 0.06 [log (Ca (++)) M], while IC50 in presence of verapamil (0.1 μM) is -1.69 ± 0.05 [log (Ca (++)) M]. Statins produced right shift in the IC50 of CCRCs. The effects of statins are like that of effects of verapamil, a standard calcium channel blocker.
  
  
  
  Our findings suggest that current statins have calcium antagonistic effects that act on voltage gated calcium channels that may provide a rationale for cause muscle weakness and gastrointestinal disorders.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan. niazpharmacist@yahoo.com.
authors.forename: Niaz
authors.initials: N
authors.lastname: Ali
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Robina
authors.initials: R
authors.lastname: Begum
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Muhammad Saleh
authors.initials: MS
authors.lastname: Faisal
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Aslam
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Nabi
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Gulfam
authors.initials: G
authors.lastname: Shehzadi
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences (IBMS), Khyber Medical University, Peshawar, Pakistan.
authors.forename: Shakir
authors.initials: S
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, Abasyn University, Peshawar, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Waqar
authors.initials: W
authors.lastname: Ali
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Atorvastatin; Fluvastatin; Rosuvastatin; Simvastatin; Statins; Verapamil; Voltage gated calcium channels