Electrophysiological effects of AFD-21 and AFD-19, new antiarrhythmic compounds on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.
(57/233)
1. The effects of AFD-21, a newly synthesized antiarrhythmic compound, and AFD-19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, AFD-21 10(-5) M caused a slight prolongation of action potential duration (APD), while AFD-19 above 10(-6) M shortened APD in a dose-dependent manner. 3. Both AFD-21 and AFD-19 above 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. 4. In the presence of AFD-21 or AFD-19, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. A time constant for the recovery of Vmax from the use-dependent block was 2.9 s for AFD-21 and 3.6s for AFD-19. 5. The curves relating membrane potential and Vmax were shifted by AFD-21 (10(-5) M), or AFD-19 (10(-5) M) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6. In single ventricular myocytes treated with AFD-21 (10(-5) M) or AFD-19 (10(-5) M), Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that both AFD-21 and AFD-19 have use- and voltage-dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics. (+info)
New antinociceptive agents related to dihydrosphingosine.
(58/233)
The main objective of this study was to evaluate the antinociceptive activity of three ethylenediamine derivatives and three beta-aminoethanol lipidic derivatives structurally related to dihydrosphingosine. These derivatives were selected on the basis of previous results from in vitro and in vivo anti-inflammatory studies. For all of the assayed compounds, an intraperitoneal dose of 3 mg/kg caused pronounced pain inhibition as measured by the acetic acid-induced writhing model in mice. Compounds 3 and 6 demonstrated strong antinociceptive activity at doses as low as 1 mg/kg and proved to be considerably more potent than the common nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) and acetaminophen (ACE). We further analyzed these compounds using the capsaicin- and glutamate-induced pain tests. Compounds 3 and 6 also exhibited considerable antinociceptive effects under these conditions, but their inhibitory effects in the formalin test were less pronounced. The exact mechanism of action for these compounds has yet to be established. However, based the results from a hot-plate test, it can be stated that these new drugs do not interact with the opioid system. (+info)
Synthesis and anti-mycobacterial activity of novel amino alcohol derivatives.
(59/233)
Diversity-oriented synthesis based on the DPPP-catalyzed mixed double-Michael reactions of electron-deficient acetylenes and beta-amino alcohols.
(60/233)
Effects of heptaminol AMP amidate (HAA) on cyclic AMP level and mitogen-induced proliferation of murine spleen cells.
(61/233)
Heptaminol AMP amidate (HAA), a nucleotide derivative, was found to elevate the intracellular cyclic AMP (cAMP) level of cultured mice spleen cells in a time- and dose-dependent manner. Theophylline and imidazole, when added to the spleen cell culture simultaneously with HAA, respectively caused a further rise and a fall of the cAMP level increased by HAA alone. When comparatively higher doses of the T cell mitogen concanavalin A (Con A) were used in the culture, Con A-induced cell proliferation was mildly inhibited in the culture of spleen cells pooled from HAA administered mice in comparison to the culture of spleen cells pooled from saline treated mice. On the other hand, when another T cell mitogen phytohemagglutinin P (PHA) was used in different concentrations in the culture, there was a trend of enhanced cell proliferation in the culture of spleen cells pooled from HAA administered mice in comparison to the responses in the culture of spleen cells pooled from saline treated mice. The present results supported the previous findings that HAA-mediated immunopotentiation was closely related with a cAMP level elevating property of HAA, and the compound also enhanced the function of helper T cells. (+info)
Development of beta-amino alcohol derivatives that inhibit Toll-like receptor 4 mediated inflammatory response as potential antiseptics.
(62/233)