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Molecularly imprinted polymers (MIPs), for the templates free base racemic propranolol and the L-enantiomer of phenylalanine anilide (L-PA), were investigated as stationary phases in supercritical fluid chromatography (SFC). Large retention differences were observed on the propranolol MIP for both the template molecule and the structural analogue metoprolol compared to that observed on the corresponding blank polymer. Mobile phase composition and solute concentration were found to affect this retention behaviour. The phenylalanine anilide MIP (L-PA MIP) was found to be enantioselective in SFC with stronger retention observed for the template enantiomer. Throughout the study, characteristic imprinting peak shapes for the stronger retained template molecule were observed for both MIPs examined. After a number of days under supercritical fluid conditions, the performance of the photochemically initiated L-PA MIP was found to significantly deteriorate whereas the thermally initiated propranolol MIP revealed only small changes in its separation performance after a long term of operation. The separation behaviour of these two MIPs in SFC was compared with results obtained on the same columns in high-performance liquid chromatography (HPLC) both before and after their application in SFC.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11128215&dopt=Abstract
Eur J Pharmacol. 1985 Aug 15;114(2):157-65.
Selective labelling of beta 1-adrenoceptors in rabbit lung membranes by (-)[3H]bisoprolol.
Wang XL, Brinkmann M, Brodde OE.
The binding properties of a newly developed, highly selective beta 1-adrenoceptor antagonist radioligand, (-)[3H]bisoprolol (EMD 33512) were investigated in rabbit lung membranes containing a mixture of 80% beta 1-and 20% beta 2-adrenoceptors. The binding of (-)[3H]bisoprolol at 25 degrees C was saturable, of high affinity (KD = 4.7 +/- 0.6 nM, N = 4), rapid and readily reversible. The maximal number of (-)[3H]bisoprolol binding sites (244 +/- 31 fmol bound/mg protein, N = 4), however, was only 80% of the number of sites labelled by the non-selective beta-adrenoceptor radioligand (-)[125I]iodocyanopindolol (299 +/- 36 fmol bound/mg protein, N = 4). beta-Adrenoceptor antagonists (non-selective: propranolol, alprenolol; beta 1-selective: metoprolol, practolol, bisoprolol; beta 2-selective: ICI 118,551) inhibited (-)[3H]bisoprolol binding with monophasic displacement curves and pseudo-Hill coefficients of 1.0 indicating that in rabbit lung membranes (-)[3H]bisoprolol labels a homogeneous class of beta-adrenoceptors. Agonists inhibited binding with an order of potency: (-)-isoprenaline greater than (-)-noradrenaline = (-)-adrenaline, which is a typical one for beta 1-adrenoceptors. It is concluded that in rabbit lung membranes (-)[3H]bisoprolol selectively labels beta 1-adrenoceptors. (-)[3H]Bisoprolol therefore seems to be a suitable ligand for direct determination of the properties of beta 1-adrenoceptors in those tissues where both beta-adrenoceptor subtypes coexist.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2864272&dopt=Abstract
Clin Pharmacol Ther. 1981 Nov;30(5):581-6.
Measurement of partial agonist activity of pindolol.
Carruthers SG, Twum-Barima Y.
The partial agonist activity of pindolol was assessed by examining the action of cumulative doses on the heart rate of resting, standing, and exercising healthy men and by studying the interaction of pindolol with metoprolol, a beta blocker devoid of partial agonist activity. Pindolol did not affect resting or standing heart rates (RHR, SHR) but reduced the heart rate after vigorous exercise by approximately 25%. The flatter dose-response curve of pindolol for exercise heart rate (EHR) has been reported from practolol and oxprenolol, which also exert partial agonist activity. After extremely large doses of pindolol there was no evidence of enhancement of agonist activity on RHR, nor was there any evidence of dominance of agonist activity over antagonist activity on EHR. Metoprolol did not alter RHR but reduced SHR by approximately 20% and EHR by approximately 31%. The effects of pindolol on SHRs and EHRs were not enhanced by metoprolol, even though the drug itself induced greater reductions of both. The reduction of SHR by metoprolol was reversed by pindolol. Pindolol appears to have greater affinity than metoprolol for atrial beta adrenoceptors in man.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7297017&dopt=Abstract
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