Effects of the (+/-)-, (+)- and (-)-forms of propranolol, timolol and metoprolol on noradrenergic transmission in the rat isolated right ventricle.
The effects of the (+/-)-, (+)- and (-)-forms of propranolol, timolol and metoprolol on noradrenergic transmission have been studied in the rat isolated right ventricle. (+)- And (-)-propranolol (10(-5) M) inhibited the accumulation of radioactivity from [3H]-noradrenaline. The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]-noradrenaline, was reduced by (+)- and (-)-propranolol (10(-5) M), (+)-timolol (10(-5) M), (-)-timolol (10(-6) - 10(-5) M) and (+)-metoprolol (10(-5) M). (+)-Propranolol, (+)-timolol (10(-6) M) and (+)- and (-)-metoprolol (10(-5) M) increased the decline in outflow of radioactivity evoked by field stimulation in the absence, but not in the presence, of lignocaine (10(-4) M), probably by decreasing nerve excitability. The ability of (-)-propranolol (10(-5) M) to increase the decline in evoked outflow was also reduced in the presence of lignocaine. (+)-Propranolol, (+)-timolol and (-)-metoprolol reduced the contractile response to field stimulation by a similar percentage in the absence or presence of lignocaine. The ability of (-)-propranolol and (+)-metoprolol (10(-5) M) to reduce contractile responses was decreased and abolished, respectively, by the addition of lignocaine. Evoked-outflow was not altered but contractile responses were inhibited by (-)-timolol (10(-7) - 10(-5) M) and (-)-metoprolol (10(-5) M). Contractile responses to isoprenaline were not altered by (+)-propranolol, (+)-timolol (10(-7) M) and (+)-metoprolol (10(-7) - 10(-6) M). (+)- Or (-)-propranolol (10(-7) M) and (+)-timolol (10(-6) M) had no effect on the rate of beating to isoprenaline but reduced the force whereas (+/-)-metoprolol (10(-7) M) had no effect on the force but reduced the rate of beating. The rate of beating and force responses to isoprenaline were reduced by (+/-)-, (+)-, (-)-propranolol (10(-6) M), (+/-)- or (-)-timolol (10(-7) - 10(-6) M), (+/-)-metoprolol (10(-6) M) and (-)-metoprolol (10(-7) - 10(-6) M). The data suggest that, in the rat isolated right ventricle, the (+)-isomers are active constituents of (+/-)-propranolol and (+/-)-timolol but not of (+/-)-metoprolol.
D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013999:Timolol / Q000494:pharmacology*; D014316:Tritium / Q000378:metabolism
D014316:Tritium; D013999:Timolol; D011433:Propranolol; D008790:Metoprolol; D009638:Norepinephrine