piperidines and bamipine

A series of compounds containing privileged scaffolds of the known histamine H(1) receptor antagonists cetirizine, mianserin, ketotifen, loratadine, and bamipine were synthesized for further optimization as ligands for the related biogenic amine binding dopamine D(3) receptor. A pharmacological screening was carried out at dopamine D(2) and D(3) receptors. In the preliminary testing various ligands have shown moderate to high affinities for dopamine D(3)receptors, for example, N-(4-{4-[benzyl(phenyl)amino]piperidin-1-yl}butylnaphthalen-2-carboxamide (19a) (hD(3)K(i)=0.3 nM; hD(2)K(i)=703 nM), leading to a selectivity ratio of 2343.

Topics: Amines; Animals; Binding, Competitive; Cell Line; Cetirizine; CHO Cells; Cricetinae; Cricetulus; Dopamine D2 Receptor Antagonists; Drug Design; Drug Evaluation, Preclinical; Histamine H1 Antagonists; Humans; Ketotifen; Ligands; Loratadine; Mianserin; Molecular Structure; Piperidines; Receptors, Dopamine D3; Stereoisomerism; Structure-Activity Relationship

Several compounds (bamipine, chlorphenoxamine, estracyt, hycanthone, quinidine, quinine, tamoxifen, trifluoperazine and verapamil) have a common basic structure with the following features: lipophilic aromatic ring system; linked chain hydrophilic N-alkyl group. They are used medically for varying diseases. Their activity in reversing multidrug-resistance (MDR) with other compounds (diethylstilbestrol, beta-estradiol, methylbiguanide, methylpiperazine, testosterone) lacking one of these chemical features is compared. The in vitro test system we used was the nucleoside incorporation assay using parental L 1210 ascites tumor cells and a doxorubicin resistant subline, which expresses the MDR phenotype. The substances lacking one of these features were not effective in reversing the MDR whereas all other tested substances demonstrated modulating potential in the MDR resistant L 1210 cells.

Topics: Animals; Drug Resistance; Ethylamines; Hycanthone; Leukemia L1210; Phenotype; Piperidines; Quinidine; Quinine; Tamoxifen; Trifluoperazine; Verapamil

The electrochemical oxidation of bamipine hydrochloride in sulphuric acid and phosphate buffer solutions was examined using a platinum electrode. Two different reaction mechanisms for two different potential regions are proposed. It was shown that the determination of the drug by this method is feasible.

Topics: Chemical Phenomena; Chemistry; Electrochemistry; Oxidation-Reduction; Piperidines

Biotransformation and Pharmacokinetics of Bamipine in Rats/2nd Communication: Pharmacokinetic studies (Part I). After oral application in Wistar rats the pharmacokinetic properties of N-phenyl-N-benzyl-4-amino-1-methylpiperidine (bamipine) were investigated. The compound is quantitatively absorbed. Bamipine distribution occurs in the whole organism. A transient accumulation was found in liver, kidney, spleen and lung. The compound's liquor patency was established. The elimination is mainly renal (85.81%), 13.23% are eliminated by feces. The total excretion after 96 h is more than 99%.

Topics: Animals; Drug Administration Schedule; Histamine H1 Antagonists; Kinetics; Male; Metabolic Clearance Rate; Piperidines; Rats; Rats, Inbred Strains; Tissue Distribution

Biotransformation and Pharmacokinetics of Bamipine in Rats/1st Communication: Biotransformation studies. The metabolism of the antihistaminic N-phenyl-N-benzyl-4-amino-1-methylpiperidine (bamipine) was investigated after oral application in Wistar rats. The major metabolites in the urine were the ether glucuronides of N-p-hydroxy-phenyl-N-benzyl-4-amino-1-methylpiperidine and of N-p-hydroxyphenyl-N-benzyl-4-amino-piperidine. Unchanged drug was not detected. In vitro studies showed, in good correlation with in vivo studies, a oxidative demethylation of bamipin.

Topics: Animals; Biotransformation; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Histamine Antagonists; Kinetics; Liver; Male; Piperidines; Rats; Rats, Inbred Strains

After oral application pharmacokinetic parameters of N-phenyl-N-benzyl-4-amino-1-methylpiperidin (bamipine) were investigated. The curve of the plasma level is characterized by two maxima. If the first maximum is neglected, the calculated elimination half-life is 9.52 h, the invasion half-life 1.03 h. The first maximum is calculated as a lag-time (1.62 h). By whole-body radiography of the animal an accumulation of activity was determined in the glandular tissues behind the eye--beside the usual accumulation of activity in liver, spleen, kidney and lung.

Topics: Administration, Oral; Animals; Autoradiography; Biotransformation; Kinetics; Male; Piperidines; Rats; Rats, Inbred Strains

Topics: Chromatography, High Pressure Liquid; Drug Stability; Piperidines; Salicylamides; Salicylanilides; Spectrophotometry, Ultraviolet; Tablets

Topics: Colorimetry; Histamine Antagonists; Piperidines; Spectrometry, Fluorescence; Tablets

Topics: Anti-Allergic Agents; Biperiden; Histamine H1 Antagonists; Humans; Parasympatholytics; Parkinson Disease; Piperidines

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Piperidines

Topics: Anti-Allergic Agents; Collapse Therapy; Disease; Histamine H1 Antagonists; Piperidines; Pleura; Pleural Diseases; Pleural Effusion

Topics: Histamine H1 Antagonists; Hypersensitivity; Immune System Diseases; Piperidines

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Piperidines; Skin

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Piperidines; Salicylanilides; Tinea

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Piperidines; Skin Diseases

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Intestines; Piperidines

Topics: Histamine H1 Antagonists; Humans; Piperidines; Pruritus

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Humans; Piperidines; Prurigo

Topics: Humans; Piperidines; Pruritus; Skin

Topics: Humans; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Rhinitis, Vasomotor

Topics: Anti-Allergic Agents; Histamine H1 Antagonists; Piperidines; Skin Diseases

Topics: Dermatology; Histamine Antagonists; Humans; Piperidines

Topics: Biological Phenomena; Heart Arrest; Histamine; Histamine Antagonists; Humans; Pheniramine; Piperidines