Computational searches for crystal structures of dioxides of group 14 elements (CO, SiO, GeO) under ultrahigh pressure.

In this study, we focused on the effect of pressure on the crystal structures of dioxides of group 14 elements, SiO, GeO, and CO. Systematic searches for their crystal structures using the artificial force induced reaction method generated 219 and 147, 102 and 63, and 148 and 76 structures for SiO, GeO, and CO, respectively, at 1 and 10 atm. At 1 atm, cristobalite-like, quartz, anatase-like, and stishovite were stable structures for SiO and GeO.

Actions of CP-060S on veratridine-induced Ca2+ overload in cardiomyocytes and mechanical activities in vascular strips.

CP-060S, (-)-(S)-2-[3,5-bis(1, 1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N-[2-(3, 4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thiazolidin- 4-one hydrogen fumarate, is a novel cardioprotective drug which is designed to prevent Ca2+ overload and cause vasorelaxation. The effects of this compound were evaluated and compared with those of CP-060R (enantiomer of CP-060S,) and diltiazem (Ca2+ channel antagonist) in a veratridine-induced model of Ca2+ overload and vasorelaxation. After 5-min superfusion of veratridine (74 microM), intracellular free calcium concentrations ([Ca2+]i) of rat single cardiomyocytes, as measured with the fura-2 procedure, were greatly elevated, from 44 +/- 5 nM to 3705 +/- 942 nM, and subsequently generated cell contracture.

Effect of KC399, a newly synthesized K+ channel opener, on acetylcholine-induced electrical and mechanical activities in rabbit tracheal smooth muscle.

1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2.

The neuroprotective effect of a potent and selective inhibitor of type I NOS (L-MIN) in a rat model of focal cerebral ischaemia.

Our newly synthesized delta-(S-methylisothioureido)-L-norvaline (L-MIN) was shown to have potent inhibitory effects on Ca(2+)-dependent and constitutively expressed neuronal nitric oxide synthase (type I NOS) when compared to other commonly recognized NOS inhibitors and produced an IC50 value of 5.7 nM. By contrast, this compound exhibited more than 40-fold weaker inhibitory effects on the other NOS isoforms.

GM-109: a novel, selective motilin receptor antagonist in the smooth muscle of the rabbit small intestine.

The pharmacological properties of the cyclic peptide Phe-cyclo[Lys-Tyr(3-tBu)-beta Ala-].trifluoroacetate (GM-109), a selective motilin antagonist, were investigated in the smooth muscle of the rabbit small intestine. GM-109 (0.

Regional and species differences in glyburide-sensitive K+ channels in airway smooth muscles as estimated from actions of KC 128 and levcromakalim.

1. The purpose of the present experiments was to elucidate the differences in actions of two K+ channel openers, KC 128 and levcromakalim, on the carbachol-induced contraction, membrane potential and 86Rb+ efflux of the dog tracheal and bronchial smooth muscles. Furthermore, we compared the effects of these agents on guinea-pig and human airway smooth muscles.

Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells.

Under conditions of cholesterol depletion and SREBP-1 accumulation, changes in the levels of sterol regulatory element binding protein(s) (SREBPs) and sterol regulated gene mRNA were studied in Hep G2 cells by RNase protection assay. Cholesterol depletion increased the expression of mRNAs for cholesterol biosynthetic enzymes and low density lipoprotein (LDL) receptor. mRNAs levels for SREBP-1c and SREBP-2 were also increased by the cholesterol depletion.

In vivo bronchodilator action of a novel K+ channel opener, KC 399, in the guinea pig.

We evaluated the in vivo bronchodilator effects of KC 399, a novel K+ channel opener. In anesthetized guinea pigs, i.v.

Action of KC-399, a newly synthesized potassium channel opener, on mechanical activity and 86Rb efflux in rat aorta.

To clarify the characteristics of KC-399, a newly synthesized potassium channel opener, we investigated the effects of KC-399 and lemakalim on the contractions induced by norepinephrine (NE 1 microM) and K+ (30 and 90 mM) and on 86Rb efflux in rat thoracic aorta. KC-399 (0.01-10 nM) and lemakalim (0.

Effects of KC 399, a novel ATP-sensitive K+ channel opener, on electrical and mechanical responses in dog tracheal smooth muscle.

The effects were observed of a newly synthesized bronchodilator, KC 339 [N-(2-cyanoethyl)-2,2-bis-fluoromethyl-6-nitro-2H-1-benzopyran-4- carbothioamide], on the electrical and mechanical properties of dog tracheal smooth muscle tissues and on accumulation of second messengers. KC 399 hyperpolarized the membrane in a concentration-dependent manner, the minimum concentration required to produce hyperpolarization being 1 nM and the maximum hyperpolarization occurring with 10 nM. The hyperpolarization was still observed in low K+ solution (< 1.

The effect of a novel benzopyran derivative, KC 399, on the isolated guinea-pig trachealis and human bronchi.

1. In isolated guinea-pig trachealis, KC 399, BRL 38227 and salbutamol suppressed the spontaneously generated tone in a concentration-dependent manner with pD2 values of 8.89 +/- 0.

Long term effects of amlodipine on organ damage, stroke and life span in stroke prone spontaneously hypertensive rats.

The long term effects of amlodipine, a new long acting Ca2+ channel antagonist on organ damage, stroke and life span, were examined in stroke prone spontaneously hypertensive rats (SHRSPs). Blood pressure of the SHRSPs increased over the first 16 weeks and reached a stable level of about 250 mmHg in controls and about 200 mmHg in the amlodipine treated group. At 15 weeks after starting amlodipine treatment, all control SHRSPs exhibited varying degrees of myocardial fibrosis, proliferative and/or necrotic vasculitis and glomerular lesions, whereas only a few animals in the amlodipine group showed slight lesions.

Spasmolytic action of nicorandil in canine conductive coronary arteries in vivo is not modified by glibenclamide.

The spasmolytic effects of nicorandil, cromakalim, and nitroglycerin on coronary arteries were investigated by angiographic technique in anesthetized dogs. With intracoronary arterial (i.a.

Antiplatelet effects of fenflumizole, a new anti-inflammatory drug, in dogs.

Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl) imidazole) was given to dogs in a single oral dose of 3 or 10 mg/kg. The plasma concentrations of fenflumizole and the two metabolites (mono- and di-demethyl forms) attained to the peak level 1-2 hr after dosing of fenflumizole, returning to near the predose levels 8 hr after the dosing. Fenflumizole (10 mg/kg) given orally significantly inhibited collagen- and ADP-induced platelet aggregations ex vivo over 4 hr after the dosing.

Antithrombotic and ulcerogenic effects of fenflumizole, a new anti-inflammatory imidazole derivative, in rats.

Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl) imidazole) was given to rats in a single oral dose of 30 mg/kg. The plasma concentration of fenflumizole reached a peak 2-3 hr after the dosing in non-fasted as well as fasted rats. Two metabolites (demethylation products) of fenflumizole were also detected in the plasma, but only in traces.

Comparison of cardiovascular effects of SGB-1534 and prazosin, selective alpha 1-adrenoceptor antagonists, in anesthetized dogs.

The cardiovascular effects of a novel antihypertensive agent, SGB-1534, and its alpha 1-adrenoceptor antagonism in the renal vasculature were investigated in anesthetized dogs and compared with those of prazosin. The doses of SGB-1534 (1-100 micrograms/kg) and prazosin (3-300 micrograms/kg) were increased by a factor of about 3 and given i.v.

Effects of nicorandil on the conductive coronary artery of the dog.

The effects of nicorandil (2-nicotinamidoethyl nitrate, SG-75) on the conductive coronary artery were studied and compared with the effects of nitroglycerin and nifedipine. In isolated perfused canine heart preparations with a support dog, nicorandil produced a decrease in the resistance of the conductive coronary artery at reduced perfusion pressures, whereas nitroglycerin had similar effects even at normal perfusion pressures. In anesthetized closed-chest dogs, nicorandil and nitroglycerin produced an increase in the diameter of the conductive coronary artery (nicorandil less than nitroglycerin).

Effects of a new anti-inflammatory imidazole derivative, fenflumizole, on platelet aggregation in the rabbit.

The antiplatelet effect of fenflumizole, compared with aspirin or ticlopidine, was examined in in vitro, ex vivo and in vivo situations of the rabbit. Unlike ticlopidine, fenflumizole and aspirin effectively inhibited in vitro the platelet aggregation elicited by arachidonate and collagen. The activity of fenflumizole was 350 times more potent than that of aspirin.

Antihypertensive effects of a novel phenylpiperazine derivative, SGB-1534, on several hypertensive models of rats.

The antihypertensive activities of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4 (1H,3H)-quinazolinedione monohydrochloride, compared with prazosin, were examined in anesthetized or conscious hypertensive rat models. In anesthetized rats, SGB-1534 administered orally (3-10 mg/kg) reduced the blood pressure and significantly inhibited the pressor response to noradrenaline, but did not affect blood pressure responses to angiotensin II, isoproterenol, histamine and acetylcholine. This compound (0.

Mechanism of the hypotensive effect of a novel phenylpiperazine derivative, SGB-1534: antagonism at alpha 1-adrenergic and 5-HT2 receptors.

The present in vivo and in vitro experiment was designed to examine the hypotensive mechanisms of 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4 (1H,3H)-quinazolinedione monohydrochloride (SGB-1534). The compound given orally significantly inhibited the pressor response to i.v.

Effects of procaine on the isolated dog coronary artery.

In order to search into the mechanism of the potassium contracture of the dog coronary artery the effects of procaine were studied in the isolated smooth muscle preparation of the dog coronary artery. Procaine is a substance which is known to specifically inhibit the calcium-induced calcium release mechanism. A dose-related relaxation of the potassium contracture was observed with procaine.

Comparative effects of nicorandil and nitroglycerin on tracheal and vascular smooth muscle in the dog, in vivo and in vitro.

The effects of nicorandil (NCR) on tracheal and vascular smooth muscle in the dog were compared with those of nitroglycerin (NTG) in in vitro and in vivo preparations. In the isolated tracheal strip and coronary artery preparations contracted with KCl (30 mM), the ability of NCR to relax these muscles and arteries by 50% was 1/10-1/15 as potent as NTG. In blood-perfused tracheal preparations, single doses of NCR and NTG injected into the tracheal artery produced dose-related decreases in the intraluminal pressure (ILP) of the trachea (relaxation) and increases in the tracheal blood flow (TBF).

Effects of a new antianginal agent, nicorandil, on normoxic and anoxic contractions in isolated miniature pig coronary arteries exposed to 5-hydroxytryptamine and norepinephrine: comparison with nitroglycerin and diltiazem.

Nicorandil, nitroglycerin and diltiazem effects on normoxic and anoxic contractile responses to 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were compared in isolated miniature pig coronary artery strips. Anoxia augmented contractile responses of the strips to 5-HT and NE. Nicorandil and nitroglycerin inhibited the normoxic contractile responses to 5-HT and NE and the further contraction induced by subsequently imposed anoxia.