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W Soudijn

Publications and source records attributed to W Soudijn.

At least 73 records · Page 4Linked to original sources
PubMed1982

Halopemide and benzodiazepine binding sites.

Halopemide inhibits 3H-BZ binding to crude and washed rat forebrain membranes with IC50 values of 16-25 microM. Its putative metabolites are considerably less active. The actions of halopemide are probably not directly related to its ability to interfere with high-affinity 3H-GABA binding sites. However, halopemide may have some unique properties in this regard.

Animals↗
PubMed1981

Relationships between structure and alpha-adrenergic receptor affinity of clonidine and some related cyclic amidines.

The inhibition of specific [3H]clonidine binding to alpha-adrenergic receptors in rat brain has been studied for 43 compounds structurally related to clonidine. Oxymetazoline was found to be the most potent compound in displacing [3H]clonidine from its binding sites. 2-Methylimidazoline, 1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline and heterocyclic N-methyl-substituted compounds showed no affinity at all for [3H]clonidine receptor sites. There was a good correlation between hypotensive activity and alpha 2-adrenergic receptor affinity to some 2-(phenylamino)imidazolidines. Parallelisms between Ki's and pharmacological activities were also observed for other compounds. Apparent structural requirements for alpha 2-receptor affinity were the presence of an aromatic moiety and a N-hydrogen in the heterocyclic ring. Ortho substitution in the phenyl ring was necessary for high affinity. Compounds with an oxazolidine ring had approximately similar affinities for the [3H]clonidine binding sites compared with the corresponding imidazolines (except for the 2,6-dichlorophenyl-substituted compound) whereas the pyrrolidine derivatives showed a 10-fold weaker affinity. [3H]Clonidine sites showed a homogeneous character. KD values from saturation and displacement experiments were in good agreement with one another (2.6 and 2.7 nM, respectively) and with values in the literature.

Amidines↗
PubMed1981

Opiate receptor interaction of compounds derived from or structurally related to fentanyl.

The opiate receptor affinity of compounds derived from or structurally related to fentanyl (1) was determined by in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl g in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl g in vitro receptor binding assays. The relatively high affinity of fentanyl (3 times morphine) was hardly influenced by the introduction of a 2-CH3, 2-OCH3, or a 2-Cl substituent into the anilino phenyl and was moderately reduced by 2-C2H5, 2-OC2H5, and 2,6-(CH3)2 substitution in this ring. Removal of the n-propionyl group of the 2-OCH3 derivative, fixation of the anilino phenyl in fentanyl to the propionyl group or the piperidine ring, and replacement of the amide N by C all caused a sharp decline of receptor affinity. Examination of molecular models seemed to indicate that optimal opiate receptor interaction of fentanyl and its derivatives requires a virtually perpendicular position of the anilino phenyl with respect to the amide function.

Animals↗
PubMed1980

Effects of halopemide on potassium-induced release of radiolabeled neurotransmitters from rat cerebrocortical slices in vitro.

The effects of halopemide on the release of 3H-serotonin, 3H-noradrenaline, 3H-acetylcholine and 3H-GABA from rat frontal cortical slices in vitro were studied and compared to those of its neuroleptic congener R29800, spiperone and haloperidol. Spontaneous 3H-serotonin and to a lesser extend 3H-noradrenaline outflow were augmented by the agents, while the effects on basal 3H-acetylcholine and 3H-GABA release were small or absent. Mechanism explaining these effects are discussed. Depolarization-induced release of serotonin was affected more markedly than the extra overflow of other radiolabeled transmitters, but the statistical significant of the response was limited.

Acetylcholine↗
PubMed1979

The regional localization of R28935 in the cat brain as dependent on the route of administration.

Intravenous injection of the antihypertensive agent R2835 and its pharmacologically less active threo-isomer R29814 resulted in a distribution profile in the cat brain which differed from the regional localization after administration via the left vertebral artery. Although the two isomers had the same physico-chemical properties, R28935 penetrated more readily into the CNS. Intravenous administration resulted in almost equal levels in all brain parts, whereas after injection into the vertebral artery caudal structures contained more of both compounds that rostral structures. Differences existed between the concentrations in homotopic brain areas, especially in the brain stem. From comparison of the levels of R28935 after injection of an equiactive dose either i.v. or into the vertebral artery it is tempting to speculate that the mesencephalic tegmentum, the nucleus of the solitary tract, the inferior colliculi and/or the locus coeruleus are possible sites of the hypotensive action.

Animals↗
PubMed1979

Effects of halopemide, a new psychotropic agent, on the uptake of serotonin by blood platelets.

The influence of halopemide, a new psychotropic agent, and some putative metabolites on the uptake of 14C-5-HT into blood platelets of rat and man were studied and compared to the effects of imipramine, sulpiride and clozapine. Halopemide, its putative metabolites R 38570 and R 29676 and sulpiride inhibited the uptake in a dose-dependent manner, but the compounds were less active than imipramine. Clozapine and p-fluorohippuric acid, another putative metabolite of halopemide, were totally devoid of activity.

Animals↗
PubMed1978

Regional localization of halopemide, a new psychotropic agent, in the rat brain.

Halopemide is a new psychotropic agent, structurally related to the neuroleptics of the butyrophenone type, but with a different phamacological and clinical profile. The concentration of halopemide in the rat brain is about 10 times less than that of R29800, its chemical congener and of spiperone, both typical neuroleptics. In the pituitary gland, however, the levels are the same. The distribution profile of halopemide in rat brain deviates from that of neuroleptics. The highest level of halopemide is found in septal and thalamic areas whereas the neuroleptics are concentrated in the caudate nucleus, the nucleus accumbens and the tuberculum olfactorium. Subcellular distribution experiments show that in the caudate nucleus halopemide is far less particle-bound that are the neuroleptic agents.

Animals↗
PubMed1977

The regional localisation of a new potent centrally acting antihypertensive agent R 28935 and its less active threo-isomer R29814 in the cat brain.

Systemic administration of the centrally acting antihypertensive agent R 28935 to cats resulted in a long lasting decrease of mean arterial pressure (+/-30%) whereas the same dose of the threo-isomer R 29814 was ineffective. The antihypertensive activity was due to the unaltered drug. In spite of an identical log P, pKa, dose and a comparable plasma level, the concentration of R 28935 in all the brain areas tested was about twice that of the threo-isomer, suggesting a stereoselective uptake and/or binding of R 28935.

Animals↗