The molecular mode of action of the Ca agonist (?) BAY K 8644 on the cardiac Ca channel

1993 ◽  
Vol 424 (3-4) ◽  
pp. 343-353 ◽  
Author(s):  
M. Bechem ◽  
H. Hoffmann
Keyword(s):  
Mode Of Action ◽  
Bay K 8644 ◽  
Ca Channel ◽  
Molecular Mode ◽  
Ca Agonist

scholarly journals Internal and external effects of dihydropyridines in the calcium channel of skeletal muscle.

1990 ◽  
Vol 95 (1) ◽  
pp. 1-27 ◽  
Author(s):  
H H Valdivia ◽  
R Coronado
Keyword(s):  
Skeletal Muscle ◽  
Lipid Bilayers ◽  
Radioligand Binding ◽  
Quantitative Agreement ◽  
Bay K 8644 ◽  
Single Channels ◽  
Ca Channel ◽  
Ca Channels ◽  
Receptor Sites ◽  
Internal Side

The agonist effect of the dihydropyridine (DHP) (-)Bay K 8644 and the inhibitory effects of nine antagonist DHPs were studied at a constant membrane potential of 0 mV in Ca channels of skeletal muscle transverse tubules incorporated into planar lipid bilayers. Four phenylalkylamines (verapamil, D600, D575, and D890) and d-cis-diltiazem were also tested. In Ca channels activated by 1 microM Bay K 8644, the antagonists nifedipine, nitrendipine, PN200-110, nimodipine, and pure enantiomer antagonists (+)nimodipine, (-)nimodipine, (+)Bay K 8644, inhibited activity in the concentration range of 10 nM to 10 microM. Effective doses (ED50) were 2 to 10 times higher when HDPs were added to the internal side than when added to the external side. This sidedness arises from different structure-activity relationships for DHPs on both sides of the Ca channel since the ranking potency of DHPs is PN200-110 greater than (-)nimodipine greater than nifedipine approximately S207-180 on the external side while PN200-110 greater than S207-180 greater than nifedipine approximately (-)nimodipine on the internal side. A comparison of ED50's for inhibition of single channels by DHPs added to the external side and ED50's for displacement of [3H]PN200-110 bound to the DHP receptor, revealed a good quantitative agreement. However, internal ED50's of channels were consistently higher than radioligand binding affinities by up to two orders of magnitude. Evidently, Ca channels of skeletal muscle are functionally coupled to two DHP receptor sites on opposite sides of the membrane.

Endothelin and Ca++ agonist bay K 8644: Different vasoconstrictive properties

1988 ◽  
Vol 156 (1) ◽  
pp. 186-192 ◽  
Author(s):  
Michel Auguet ◽  
Sylvie Delaflotte ◽  
Pierre-Etienne Chabrier ◽  
Eduardo Pirotzky ◽  
François Clostre ◽  
...  
Keyword(s):  
Bay K 8644 ◽  
Ca Agonist

Monepantel: the most studied new anthelmintic drug of recent years

Parasitology ◽  
2014 ◽  
Vol 141 (13) ◽  
pp. 1686-1698 ◽  
Author(s):  
L. LECOVÁ ◽  
L. STUCHLÍKOVÁ ◽  
L. PRCHAL ◽  
L. SKÁLOVÁ
Keyword(s):  
Mode Of Action ◽  
Aquatic Organisms ◽  
Similar Efficacy ◽  
Gastrointestinal Nematodes ◽  
Soil Microflora ◽  
Parent Molecule ◽  
Important Species ◽  
Anthelmintic Drug ◽  
Reported Data ◽  
Molecular Mode

SUMMARYMonepantel (MOP), a new anthelmintic drug from a group of amino-acetonitrile derivatives, has been intensively studied during last years. Many authors examined this new drug from different perspectives, e.g. efficacy against different species and stages of parasites, mode of action, metabolism, pharmacokinetics, toxicity, resistance, ecotoxicity, etc. MOP is an anthelmintic for livestock (currently only sheep and goats), with molecular mode of action which is different to all other anthelmintics. MOP has a broad-spectrum of activity against gastrointestinal nematodes of sheep, including adults and L4 larvae of the most important species. The key feature of MOP is its full effectiveness against strains of nematodes resistant to benzimidazoles, levamisole, macrocyclic lactones and closantel. After oral administration, MOP is quickly absorbed into the bloodstream and quickly metabolized to MOP sulfone that has a similar efficacy as the parent molecule. Several other MOP metabolites formed in ovine hepatocytes were described. MOP and its metabolites are considered to be non-toxic to environment and its components, such as soil microflora, aquatic organisms, dung organisms, vegetation, etc. The aim of the presented review was not to collect all reported data but to bring an overview of various approaches in the study of MOP and to evaluate their principal results.

Morpho-physiological Effects and Molecular Mode of Action of Mepiquat Chloride Application in Cotton: A Review

2020 ◽  
Vol 20 (4) ◽  
pp. 2073-2086
Author(s):  
Shahbaz Atta Tung ◽  
Ying Huang ◽  
Abdul Hafeez ◽  
Saif Ali ◽  
Anda Liu ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Physiological Effects ◽  
Mepiquat Chloride ◽  
Molecular Mode

Comparative Effects of Bupivacaine and Ropivacaine on Intracellular Calcium Transients and Tension in Ferret Ventricular Muscle

2004 ◽  
Vol 101 (4) ◽  
pp. 888-894 ◽  
Author(s):  
Yasushi Mio ◽  
Norio Fukuda ◽  
Yoichiro Kusakari ◽  
Yoshikiyo Amaki ◽  
Yasumasa Tanifuji ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Bay K 8644 ◽  
Clinical Settings ◽  
Ca Channel ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Intracellular Ca ◽  
Slope Difference ◽  
The Relationship

Background Recent evidence suggests that ropivacaine exerts markedly less cardiotoxicity compared with bupivacaine; however, the mechanisms are not fully understood at the molecular level. Methods Isolated ferret ventricular papillary muscles were microinjected with the Ca-binding photoprotein aequorin, and intracellular Ca transients and tension were simultaneously measured during twitch in the absence and presence of bupivacaine or ropivacaine. Results Bupivacaine and ropivacaine (10, 30, and 100 microm) reduced peak systolic [Ca]i and tension in a concentration-dependent manner. The effects were significantly greater for bupivacaine, particularly on tension (approximately twofold). The percentage reduction of tension was linearly correlated with that of [Ca]i for both anesthetics, with the slope of the relationship being approximately equal to 1.0 for ropivacaine and approximately equal to 1.3 for bupivacaine (slope difference, P < 0.05), suggesting that the cardiodepressant effect of ropivacaine results predominantly from inhibition of Ca transients, whereas bupivacaine suppresses Ca transients and the reaction beyond Ca transients, i.e., myofibrillar activation, as well. BAY K 8644, a Ca channel opener, abolished the inhibitory effects of ropivacaine on Ca transients and tension, whereas BAY K 8644 only partially inhibited the effects of bupivacaine, particularly the effects on tension. Conclusion The cardiodepressant effect of bupivacaine is approximately twofold greater than that of ropivacaine. Bupivacaine suppresses Ca transients more markedly than does ropivacaine and reduces myofibrillar activation, which may at least in part underlie the greater inhibitory effect of bupivacaine on cardiac contractions. These results suggest that ropivacaine has a more favorable profile as a local anesthetic in the clinical settings.

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