piperidines and clidinium

It was previously found that alcuronium increases the binding of [3H]methyl-N-scopolamine to cardiac muscarinic receptors by a positive allosteric action while its effect on the binding of [3H]quinuclidinyl benzilate is negative. The, features of the antagonist's molecule which decide whether its allosteric interaction with alcuronium is positive or negative are not known. In the present work, it was found that alcuronium has a positive allosteric effect also on the binding of [3H]atropine and [3H]methyl-N-piperidinyl benzilate to muscarinic receptors in rat heart atria and that its effect on the binding of [3H]methyl-N-quinuclidinyl benzilate is negative. A comparison of the five radiolabelled antagonists that have been investigated so far indicates that the type of allosteric interaction (positive or negative) is not determined by the presence or absence of the quaternary nitrogen or of the benzilyl moiety in the molecule of the antagonist. Apparently, features of the N-bearing moiety of muscarinic antagonists other than the presence of a charge on nitrogen play a key role in the determination of the type of interaction.

Topics: Alcuronium; Allosteric Regulation; Animals; Atropine; Benzilates; In Vitro Techniques; Male; Muscarinic Antagonists; Myocardium; Piperidines; Quinuclidinyl Benzilate; Rats; Rats, Wistar; Receptors, Muscarinic

Seventy Syrian golden hamsters bearing SC transplants of Greene melanoma were used to evaluate the degree of tumour uptake of several 11C-radiopharmaceuticals selected for their potential specificity for melanoma. Tissue distribution studies were performed at 30 and 60 min after IV injection of 11C-compounds and compared with the 24-h uptake of 67Ga-citrate. Gamma camera images were also compared. The highest tumour uptake at 1 h was observed with 11C-methionine (2.42% +/- 0.72%) and although activity in liver, spleen and kidney exceeded that in melanoma the tumour was demonstrated on gamma camera imaging. Melanoma localisation of 11C-chlorpromazine, 11C-flunitrazepam and 11C-ketanserine was comparable at 1% of the dose injected per gram of tumour. High activity in other organs, particularly liver, exceeded uptake in melanoma and attempts at tumour imaging were unsuccessful. Tumour accumulation of 11C-methiodide quinuclidinyl benzylate (MQNB), an 11C-imidazobenzodiazepine (Ro-15-1788) and 14C-pimozide was low and imaging studies were not attempted. None of the 11C-radiopharmaceuticals evaluated for melanoma affinity matched that of 67Ga-citrate. The 24-h tumour uptake of 67Ga-citrate was 4.07% +/- 1.37% dose injected per gram which allowed delineation of the melanoma by gamma camera imaging.

Topics: Animals; Benzodiazepinones; Carbon Radioisotopes; Chlorpromazine; Cricetinae; Flumazenil; Flunitrazepam; Gallium Radioisotopes; Isotope Labeling; Ketanserin; Melanoma; Mesocricetus; Methionine; Neoplasm Transplantation; Pimozide; Piperidines; Quinuclidinyl Benzilate; Radionuclide Imaging; Tissue Distribution