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Biomedical subjects

C Martini

Publications and source records attributed to C Martini.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effects of substituent size upon adenosine receptor A1/A2 affinity of some newly synthesised 8-cycloalkyl xanthines.

The activity of a series of 1,3-dipropyl-xanthines bearing C8-cycloalkyl substituents as antagonists at A1 and A2 adenosine receptors is examined. Pharmacological results showed that the size of the 8-substituent is an important feature for response in activity of such class of antagonists. Among compounds 3-8, the 2-norbornyl analog 6 showed the best A1/A2 selectivity. A new route for the synthesis of 8-alkyl-substituted xanthines is presented. This method, consisting of a direct alkylation of the imidazole moiety through a radical mechanism reaction, was shown to be a more convenient strategy in comparison with the commonly employed synthetic schemes.

Animals↗
PubMed1994

Structure-activity relationships of 1,2,4-triazolo[1,5-a] quinoxalines and their 1-deaza analogues imidazo[1,2-a]quinoxalines at the benzodiazepine receptor.

The synthesis, BZR binding activity, and GABA ratio of some 1,2,4-triazolo[1,5-a]quinoxalines and imidazo[1,2-a]quinoxalines are reported. Both series of compounds displayed similar affinities while their efficacies were different. The structure-activity relationships have provided the opportunity to localize on the BZR accessory areas which are able to enhance the affinity and evaluate the importance of the presence or absence of a proton acceptor atom to determine different trends of efficacy.

Animals↗
PubMed1994

8-Azaxanthine derivatives as antagonists of adenosine receptors.

A series of 1,3-dimethyl- and 1,3-dipropyl-8-azaxanthines, substituted at the N8 or N7 position with substituents which usually increase the affinity of the xanthines for the adenosine receptors, was synthesized and studied in radioligand binding experiments. The substitution of CH with N at the 8-position of both theophylline and caffeine dramatically reduced the affinity, as demonstrated by the fact that 8-azatheophylline and 8-azacaffeine were inert. The introduction of a methyl group at 8-position of 8-azatheophylline restored the antagonistic activity at A2 receptors, while a 8-cycloalkyl substituent increased the affinity for both receptor subtypes. A more favorable effect on affinity was produced by the substitution of the 7-methyl group in 8-azacaffeine with cycloalkyl groups. 7-Cyclopentyl-1,3-dimethyl-8-azaxanthine was 3 times more potent than caffeine at A1 receptors and 6 times less active at A2 receptors. On the contrary, the 7-cyclohexyl-1,3-dimethyl-8-azaxanthine was more potent than caffeine at A2 receptors. The substitution of 1- and 3-methyl groups with propyl in both 7- and 8-substituted 8-azatheophylline increased remarkably the affinity for A1 receptors. The 7-cyclopentyl-1,3-dipropyl-8-azaxanthine appears to be one of the most potent and selective among 7-alkyl-substituted xanthines at A1 receptors so far known. Because the 8-aza analogues of 8-substituted 1,3-dialkylxanthine were in any case less active than the corresponding xanthine derivatives, it was confirmed that the hydrogen atom at the 7-position of xanthines plays an important role in the binding to adenosine receptors.

Animals↗
PubMed1994

Characterization of peripheral-type benzodiazepine binding sites from rat and pig pancreas.

The binding of [3H]1-(2-chlorophenyl-N-methyl-1-methyl-propyl)-3-isoquinolinecarboxa mide ([3H]PK-11195) and [3H]7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4-benzodiaz epin-2 - on ([3H]Ro5-4864) to membrane preparations of pancreas was studied in the rat and pig. [3H]PK-11195 bound with high affinity to rat and pig membrane preparations yielding maximal numbers of binding sites (Bmax) of 2393 +/- 160 and 777 +/- 65 fmol/mg of protein, respectively, and equilibrium dissociation constant (Kd) values of 3.01 +/- 0.25 and 3.9 +/- 0.23 nM, respectively. [3H]Ro5-4864 successfully labelled rat but not pig pancreatic membranes, yielding a Kd value of 6.45 +/- 0.5 nM and a Bmax value of 551 +/- 43 fmol/mg of protein. Displacement studies showed a similar rank order of potency of various unlabelled ligands against both [3H]Ro5-4864 and [3H]PK-11195 binding to rat and pig membrane preparations (PK-11195 > or = Ro5-4864 > diazepam > flunitrazepam >> flumazenil). These results suggest that [3H]PK-11195 binds with high affinity and specificity to rat and pig pancreas and [3H]Ro5-4864 binds with high affinity and specificity to rat but not pig pancreas.

Animals↗
PubMed1994

The [(methyloxy)imino]methyl moiety as a bioisoster of aryl. A novel class of completely aliphatic beta-adrenergic receptor antagonists.

Previous studies in the field of beta-adrenergic drugs had supported the hypothesis of the existence of a bioisosterism between the [(methyleneamino)oxy]methyl moiety (C = NOCH2, MAOMM) of type B beta-blocking drugs and the aryl (Ar) of type A beta-blocking agents. In the MAOMM, however, the carbon of the CH2 linked to the oximic oxygen possesses a hybridization (sp3) and a geometry different from those of the corresponding carbon of Ar which possesses an sp2 hybridization. Furthermore, in the MAOMM, in its preferred conformation, the unsaturated portion (C = N) is situated in a spatial area which does not correspond exactly to the area occupied by Ar. The formal inversion of the atomic sequence C = NOCH2 of the MAOMM leads to a different type of group, the [(methyloxy)imino]methyl moiety (CH2ON = C, MOIMM), which, in the E configuration, appears to present greater steric and electronic analogies with an Ar, with respect to the MAOMM. On the basis of these observations, some completely aliphatic (E)-N-(3-amino-2- hydroxypropylidene)(alkyloxy)amino derivatives of type C (11a,b and 12a, b) were synthesized, the their beta-adrenergic properties were compared with those of the corresponding [(methyleneamino)oxy]-methyl isomers of type B (19a, b and 20a, b). The similar beta-adrenergic properties of 11, 12 and 19, 20 evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations, are discussed on the basis of considerations regarding the spatial correspondences and electronic analogies between the MOIMM and the MAOMM.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1994

Solubilization and characterization of [3H]imipramine and [3H]paroxetine binding sites from calf striatum.

The serotonin (5-HT) transporter from calf striatum cerebral membranes was solubilized with digitonin and characterized by gel exclusion chromatography. [3H]Imipramine and [3H]paroxetine were utilized as markers for labeling it. 3H-imipramine labels a high- and a low-affinity site on striatum membranes, whereas it binds to a single high-affinity site on the solubilized fraction. [3H]Paroxetine binds with the same affinity to a single site on both membranes and solubilized preparations. After gel exclusion chromatography of the solubilizate both [3H]imipramine and [3H]paroxetine bind on an identical fraction of 205 kDa molecular weight, with a similar maximum number of binding sites (Bmax). Our results suggest that both 3H-imipramine and [3H]paroxetine bind to a common site on the 5-HT transporter.

Animals↗
PubMed1994

Organic brain syndromes and opioid administration for cancer pain.

To clarify the range of potential etiologies that may contribute to organic brain syndrome in patients receiving systemic opioids for cancer pain, we describe 15 patients who presented this complication. In 11 cases, concomitant conditions were found that could contribute to the onset of organic brain syndrome. These data illustrate that multiple causes often play a role in the development of mental status changes in advanced cancer. Opioids are seldom the only causal factor implicated.

Aged↗
PubMed1994

Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report.

We evaluated the local and systemic tolerability of ketorolac administered through continuous subcutaneous infusion in ten cancer patients. The patients were monitored daily for the severity and duration of pain, and the development of other symptoms. The duration of injection site varied from 1 to more than 7 days. No patients complained of local discomfort or pain. Mild local bleeding at the site of drug injection was observed in seven cases. No increase in the intensity of symptoms was observed during the infusion of ketorolac.

Adult↗
PubMed1994

Changes in peripheral benzodiazepine receptors in patients with panic disorder and obsessive-compulsive disorder.

Peripheral benzodiazepine (BDZ) receptors were investigated through the binding of the specific ligand 3H-PK-11195 to platelet membranes, in 17 patients suffering from panic disorder (PD) and in 16 patients affected by obsessive-compulsive disorder (OCD). The results, showing that the density (Bmax) of peripheral BDZ receptors was significantly lower in patients with PD than in controls or OC patients, suggest that the number of platelet BDZ receptors varies with different anxiety disorders and that perhaps this marker may be beneficial in differentiating some subtypes of these disorders.

Adolescent↗
PubMed1994

3H-NECA binding to polymorphonuclear membrane: effect of sera from patients with Hodgkin's disease.

Several studies have shown that sera from patients with Hodgkin's disease contain factors capable of inhibiting polymorphonuclear functions, among them chemotaxis. In the present study, we investigated whether these sera, which were able to inhibit PMN chemotaxis in the agarose test, were also able to affect the 3H-NECA binding to PMN membrane obtained from healthy donors. Control experiments were carried out using PMN incubated with a pool of sera from healthy volunteers. No significant difference was found in the maximum number of binding sites; on the contrary, the equilibrium dissociation constant was significantly increased in the membrane preparation of PMN incubated with pathological serum.

Adenosine↗
PubMed1994

[Giacomo Andrea Diacomini, the medical systems and the origins of experimental pharmacology].

Giacomo Andrea Ciacomini was Professor of Physiology, Pathology and General Therapeutics in the University of Padua (1824-1849); follower of systematic medicine, he followed vitalistic theories. For him diagnosis-identification of diseases and therapy are closely related and diseases are due to an excess or a loss of stimulations. About quinine, generally administered in fevers at high doses as a tonic-stimulant drug, Giacomini believed that it has a depressant activity, an action verified by him on rabbits, an early example of exerimental pharmacology in Italy (1840). Thus, Giacomini performed empirical studies, and the real differences between systematic and scientific medicine are in the different approach to the relationship between empirical observations and theoretical hypotheses.

History, 19th Century↗
PubMed1994

Synthesis and benzodiazepine receptor activity of some 4,5-dihydro-1H-pyrazolo[4,3-c][1,8]naphthyridine derivatives.

The preparation of 5-substituted 1-aryl-4,5-dihydro-1H-pyrazolo[4,3- c][1,8] naphthyridines by reaction of 5-substituted 3-hydroxymethylene-2,3-dihydro-1,8-naphthyridin-4(1H)-ones with various phenylhydrazines is described. The benzodiazepine binding activity of these compounds was evaluated in vitro. Only the 5-methyl substituted derivatives showed affinity for the benzodiazepine receptor, with K1 values ranging from 2.9 to 0.195 microM for the para-phenyl substituted compounds. A hypothesis of interaction of these ligands with the receptor site is reported.

Animals↗
PubMed1994

2-Aryl-8-azaadenosines: structure-activity relationships in the binding with A1 and A2 receptors. A comparison with the corresponding 9-benzyl-8-azaadenines. III.

Several title compounds were assayed to determine their relative affinity towards the adenosine receptors. Selectivity ratios (SR) showed a prevalent A1 affinity. The comparison with the selectivity ratios of the corresponding 9-benzyl-8-azaadenines and the comparison between the affinity constant values (K1) for each receptor of the two series, were performed. The results led us to conclude that A1 receptors are characterized by more different arrangements which regard especially to 9-benzyl-8-azaadenines.

Adenine↗