Drugs online research references
Nippon Yakurigaku Zasshi. 1979 Oct;75(7):707-20.
[Pharmacological properties of dl-2-(3'-t-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'-thienyl) thiazole hydrochloride (S-596), a new beta-adrenergic blocking agent (author's transl)]
[Article in Japanese]
Hara Y, Sato E, Miyagishi A, Aono S, Nakatani H.
We developed a new beta-adrenergic blocking, antiarrhythmic compound S-596 and compared the findings with those of propranolol or practolol. S-596 antagonized the positive chronotropic and inotropic actions of adrenaline in isolated guinea-pig atria, and blocked the relaxant response to adrenaline of isolated guinea pig tracheal strips. In anesthetized mongrel dogs, S-596 given intravenously inhibited increases in heart rate and myocardial contractile force and decreases in systemic blood pressure induced by isoproterenol. In conscious dogs, the oral administration of S-596 reduced the isoproterenol induced tachycardia and the maximal effect was attained one hour after administration. In this regard S-596 was about 5 times more potent than propranolol, and S-596 was significantly longer-acting than propranolol. Thus, S-596 has greater beta-blocking activity than propranolol. S-596 has a lesser degree of myocardial depressant action than propranolol in spontaneously contracting rat or guinea pig atria and no intrinsic sympathomimetic activity in reserpinized rats. S-596 also has a weaker local anesthetic and antiarrhythmic activity than propranolol, as determined in guinea pigs and rabbits.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=94296&dopt=Abstract
Am J Physiol. 1995 May;268(5 Pt 2):H2024-35.
Electrophysiological effects of alpha 2-adrenergic stimulation in canine cardiac Purkinje fibers.
Samson RA, Cai JJ, Shibata EF, Martins JB, Lee HC.
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City 52242, USA.
The effects of alpha 2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 microM l-norepinephrine + 0.5 microM dl-propranolol (NE+P) from baseline values of 166 +/- 7 and 249 +/- 9 (SE) ms (n = 7) to 174 +/- 7 and 265 +/- 9 ms, respectively (P < 0.05 for both). Selective alpha 2-blockade with 0.01 microM yohimbine (YO) reduced this prolongation by NE+P in APD50 and APD90 to 169 +/- 7 and 256 +/- 8 ms, respectively (P < 0.05 compared with NE+P). Additional selective alpha 1-blockade with 0.01 microM prazosin (PZ) completely blocked the effects of NE+P, returning APD50 and APD90 to 163 +/- 7 and 250 +/- 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 microgram/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 +/- 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE+P, but the effects of PZ were intact. The effects of alpha 2-stimulation on beta-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE+PZ (beta- + alpha 2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE+PZ+YO (unopposed beta-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under beta-stimulation, could no longer be elicited in the presence of beta- + alpha 2-stimulation. These results suggest that the postjunctional alpha 2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by beta-adrenergic stimulation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7771552&dopt=Abstract
Neurosci Behav Physiol. 1995 Jan-Feb;25(1):1-6.
Influence of norepinephrine, acetylcholine, and their blockers on the activity of cortical neurons in goal-directed behavior.
Andrianov VV.
I. M. Sechenov Medical Academy, Moscow.
The neurochemical mechanisms of the central organization of sequential stages in the formation of a goal-directed behavioral act were investigated by means of the microiontophoretic application of biologically active substances to individual neurons of the cerebral cortex of cats. It was demonstrated that the dynamics of the discharge activity of the neurons at particular stages of the behavioral act exhibited a contradictory character when neuromediators and their antagonists were applied. At the same time, differences in the impulse activity were more pronounced against the background of the application of propranolol and atropine than of norepinephrine and acetylcholine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7777140&dopt=Abstract
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