Drugs online research references
Br J Pharmacol. 1993 Sep;110(1):369-77.
Calcium antagonist and antiperoxidant properties of some hindered phenols.
Sgaragli GP, Valoti M, Gorelli B, Fusi F, Palmi M, Mantovani P.
Istituto di Scienze Farmacologiche, Siena, Italy.
1. The calcium antagonist and antioxidant activities of certain synthetic and natural phenols, related to BHA (2-t-butyl-4-methoxyphenol), were evaluated in rat ileal longitudinal muscle and in lipid peroxidation models respectively. 2. Compounds with a phenol or a phenol derivative moiety, with the exception of 2,2'-dihydroxy-3,-3'-di-t-butyl-5,5'-dimethoxydiphenyl (di-BHA), inhibited in a concentration-dependent manner the BaCl2-induced contraction of muscle incubated in a Ca(2+)-free medium. Calculated pIC50 (M) values ranged between 3.32 (probucol) and 4.96 [3,5-di-t-butyl-4-hydroxyanisole (di-t-BHA)], with intermediate activity shown by khellin < gossypol < quercetin < 3-t-butylanisole < BHA < nordihydroguaiaretic acid (NDGA) < 2,6-di-t-butyl-4-methylphenol (BHT) and papaverine. 3. The Ca2+ channel activator Bay K 8644 overcame the inhibition sustained by nifedipine, BHA and BHT, while only partially reversing that of papaverine. 4. BHA, BHT, nifedipine and papaverine also inhibited in a concentration-dependent fashion CaCl2 contractions of muscle depolarized by a K(+)-rich medium. This inhibition appeared to be inversely affected by the Ca(2+)-concentration used. 5. The inhibitory effects of nifedipine, papaverine, BHA and BHT were no longer present when muscle contraction was elicited in skinned fibres by 5 microM Ca2+ or 500 microM Ba2+, suggesting a plasmalemmal involvement of target sites in spasmolysis. 6. Comparative antioxidant capability was assessed in two peroxyl radical scavenging assay systems. These were based either on the oxidation of linoleic acid initiated by a heat labile azo compound or on lipid peroxidation of rat liver microsomes promoted by Fe2+ ions.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7693283&dopt=Abstract
Eur J Pharmacol. 2000 Apr 7;394(1):109-15.
On the mechanisms of the antispasmodic action of some hindered phenols in rat aorta rings.
Fusi F, Marazova K, Pessina F, Gorelli B, Valoti M, Frosini M, Sgaragli G.
Istituto di Scienze Farmacologiche, Universita di Siena, via E.S. Piccolomini 170, 53100, Siena, Italy.
The antispasmodic effects of 3-t-butyl-4-hydroxyanisole (BHA) and some structurally related compounds were investigated in endothelium-intact rat aorta rings. Nordihydroguaieretic acid (NDGA), BHA, 3,5-di-t-butyl-4-hydroxyanisole (DTBHA), 2,6-di-isopropyl phenol (propofol) and 2,2'-dihydroxy-3,3'-di-t-butyl-5, 5'-dimethoxydiphenyl (DIBHA) did not cause relaxation when added at the plateau of phenylephrine-evoked contraction, nor did they affect the concentration-relaxation curve for acetylcholine in precontracted rings. In rings depolarised with physiological salt solution (PSS) containing 40 mM K(+), NDGA, BHA, DTBHA, 2, 5-di-t-butyl-1,4-benzohydroquinone (BHQ), propofol and nifedipine, but not DIBHA, inhibited the contraction induced by cumulative addition of Ca(2+) (0.05-10 mM) in a concentration-dependent manner; this inhibition was inversely related to the Ca(2+) concentration. In 40 mM K(+) PSS, 25 nM nifedipine blocked the 1 mM Ca(2+)-induced contraction, whereas 50 microM DTBHA, NDGA, BHA, BHQ and propofol significantly antagonised it by 84.4%, 73.0%, 52.8%, 45.6% and 35.7%, respectively. In the presence of 1 microM methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate (Bay K 8644), the response to Ca(2+) did not differ from control values with nifedipine and BHQ, was partially restored with DTBHA and NDGA, and was not affected with BHA and propofol. Nifedipine markedly inhibited (85.2%) the Ba(2+)-induced contraction and this effect was totally reversed by Bay K 8644. BHA and DTBHA showed antispasmodic activity (45.3% and 43.1%, respectively) which was partly reversed by Bay K 8644. In contrast, Bay K 8644 did not affect the inhibition exerted by BHQ, NDGA and propofol (69.5%, 53. 3% and 46.1%, respectively). Nifedipine, BHA, DTBHA, propofol and NDGA inhibited the contractile response to 1 mM Ca(2+) of aorta rings depolarised with 40 or 80 mM K(+) PSS to a similar extent. Cromakalim inhibited the Ca(2+)-evoked contraction only in 30 mM K(+) PSS and BHQ only in 80 mM K(+) PSS. DIBHA had no effect on this model. Cromakalim, but not BHA, stimulated 86Rb(+) efflux from ring preparations. In 80 mM K(+) PSS containing 1 microM nifedipine, only papaverine affected the phenylephrine-induced contraction. Moreover, when the rings were preincubated with 1 mM Ni(2+), the response to phenylephrine in the presence of BHQ was significantly reduced. In conclusion, we propose that BHA may non-specifically inhibit Ca(2+) influx at the plasmalemma level rather than affect the function of K(+) channels, Ca(2+) release from intracellular stores or endothelium-dependent relaxation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10771042&dopt=Abstract
J Pharm Pharmacol. 2001 Dec;53(12):1671-8.
Effects of the class III antiarrhythmic agent dofetilide (UK-68,798) on L-type calcium current from rabbit ventricular myocytes.
Paul AA, Leishman DJ, Witchel HJ, Hancox JC.
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, Bristol, UK.
The methanesulphonanilide agent dofetilide (UK-68,798) exerts Class III antiarrhythmic effects by inhibiting the cardiac rapid delayed rectifier potassium current (I(Kr)) encoded by HERG. The aim of the present study was to determine whether dofetilide also exhibits Class IV (L-type calcium-channel blocking) effects. L-type calcium current (I(Ca,L)) was measured from rabbit isolated ventricular myocytes, using the whole-cell patch-clamp technique under selective recording conditions. Positive control experiments demonstrated inhibition of I(Ca,L) elicited by pulses to + 10 mV by both nifedipine and externally applied Ni2+ ions. Three concentrations of dofetilide were tested: 100 nM, 1 microM and 10 microM. I(Ca,L) magnitude was not significantly reduced by any of the concentrations tested (P > 0.05; n = minimum of seven cells per drug concentration). The inactivation time-course of I(Ca,L) was also unaffected by 10 microM dofetilide. Heterologously expressed HERG current (I(HERG)) recorded from Chinese Hamster Ovary cells was extensively inhibited by 100 nm and 1 microM dofetilide, with inhibition at 1 microM not significantly different from 100% (P > 0.1). It is concluded that dofetilide produced no I(Ca,L) blocking effects at concentrations up to and exceeding that required for maximal I(HERG) inhibition. The findings support the notion that dofetilide is a highly selective Class III antiarrhythmic agent, devoid of Class IV antiarrhythmic activity.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11804397&dopt=Abstract
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Wellstreet online pharmacy for click-order prescription medications ||
Altace Online Pharmacy ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Insurance plans and information ||
Insurance policies for all purposes ||
Antibiotics and prescription medications online literature ||