piperidines and 1-benzylpiperidine

The complex pathophysiology of Alzheimer's disease (AD) has prompted researchers to develop multitarget-directed molecules to find an effective therapy against the disease. In this context, a novel series of N-(1-benzylpiperidin-4-yl)-5-arylisoxazole-3-carboxamide derivatives were designed, synthesized, and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro biological evaluation demonstrated that compound 4e was the best AChE (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Butyrylcholinesterase; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Humans; Isoxazoles; Molecular Docking Simulation; Molecular Structure; Neuroprotective Agents; PC12 Cells; Piperidines; Rats; Structure-Activity Relationship

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Models, Molecular; Molecular Structure; Piperidines; Structure-Activity Relationship; Ubiquitin-Specific Peptidase 7

Multitargeted hybrids of

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Brain; Drug Design; Molecular Docking Simulation; Oxadiazoles; Piperidines; Rats; Structure-Activity Relationship

Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC

Topics: Acetylcholinesterase; Blood-Brain Barrier; Chelating Agents; Cholinesterase Inhibitors; Copper; Drug Design; Humans; Inhibitory Concentration 50; Molecular Docking Simulation; Piperidines; Pyridines; Structure-Activity Relationship

Acetylcholinesterase (AChE) is the key enzyme targeted in Alzheimer's disease (AD) therapy, nevertheless butyrylcholinesterase (BuChE) has been drawing attention due to its role in the disease progression. Thus, we aimed to synthesize novel cholinesterases inhibitors considering structural differences in their peripheral site, exploiting a moiety replacement approach based on the potent and selective hAChE drug donepezil. Hence, two small series of N-benzylpiperidine based compounds have successfully been synthesized as novel potent and selective hBuChE inhibitors. The most promising compounds (9 and 11) were not cytotoxic and their kinetic study accounted for dual binding site mode of interaction, which is in agreement with further docking and molecular dynamics studies. Therefore, this study demonstrates how our strategy enabled the discovery of novel promising and privileged structures. Remarkably, compound 11 proved to be one of the most potent (0.17 nM) and selective (>58,000-fold) hBuChE inhibitor ever reported.

Topics: Alzheimer Disease; Butyrylcholinesterase; Cholinesterase Inhibitors; Click Chemistry; Drug Design; Drug Discovery; Humans; Molecular Docking Simulation; Piperidines; Structure-Activity Relationship

The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetylcholinesterase (AChE) and β-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Compounds 40 and 41 exhibited high brain permeability in the PAMPA-BBB assay, significant displacement of propidium iodide from the peripheral anionic site (PAS) of AChE, and were devoid of neurotoxicity towards SH-SY5Y neuroblastoma cell lines up to the maximum tested concentration of 80 μM. Meanwhile, both these compounds inhibited self- and AChE-induced Aβ aggregation in thioflavin T assay, which was also re-affirmed by morphological characterization of Aβ aggregates using atomic force microscopy (AFM). Moreover, 40 and 41 ameliorated the scopolamine-induced cognitive impairment in elevated plus and Y-maze experiments. Ex vivo and biochemical analysis established the brain AChE inhibitory potential and antioxidant properties of these compounds. Further, improvement in Aβ

Topics: Alzheimer Disease; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Blood-Brain Barrier; Cell Line, Tumor; Cholinesterase Inhibitors; Cognitive Dysfunction; Drug Design; Humans; Mice; Piperidines; Protein Aggregation, Pathological; Structure-Activity Relationship

A series of fifteen acetylcholinesterase inhibitors were designed and synthesised based upon the previously identified lead compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (5) which showed good inhibitory activity (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Butyrylcholinesterase; Cell Line, Tumor; Cell Survival; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Eels; Horses; Humans; Models, Molecular; Molecular Structure; Piperidines; Structure-Activity Relationship

Two series of 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers were designed based on structure-activity relationship (SAR) and docking model of reported monoamine neurotransmitters reuptake inhibitors. The compounds were synthesized in 3-simple steps and their biological activities were evaluated. Several compounds were proven to be potent inhibitors of serotonin and norepinephrine reuptake. Computer docking was performed to study the interaction of the most potent compound 35 with human serotonin transporter. The results of the analyses suggest that 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers might be promising antidepressants worthy of further studies.

Topics: Antidepressive Agents; Drug Design; HEK293 Cells; Humans; Molecular Docking Simulation; Norepinephrine; Piperazine; Piperidines; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin and Noradrenaline Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Although carbon dioxide (CO

Topics: Amino Acids; Carbon Dioxide; Catalysis; Free Radicals; Models, Chemical; Molecular Structure; Oxidation-Reduction; Photochemistry; Piperidines; Terphenyl Compounds; Ultraviolet Rays

A new family of AChE inhibitors, N-benzylpiperidines, showed exceptional efficacy in vitro and in vivo, minimal side effects and high selectivity for acetylcholinesterase (AChE). Three regression methods were chosen in this work to develop robust predictive models, namely multiple linear regression (MLR), genetic function approximation (GFA) and multilayer perceptron network (MLP). Ten descriptors were selected for a dataset of 99 molecules, using a genetic algorithm. The best results were obtained for MLP with a 10-6-1 artificial neural network model trained with the Broyden-Fletcher-Goldfarb-Shanno (BFGS) algorithm. Statistical prediction for MLR and GFA were r

Topics: Algorithms; Cholinesterase Inhibitors; Neural Networks, Computer; Piperidines; Quantitative Structure-Activity Relationship

Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine-tetrazoles. Thirty-one compounds were synthesized and evaluated for their triple reuptake inhibition of serotonin, norepinephrine and dopamine. Triple reuptake inhibitor, compound 2q, in particular, showed potent serotonin reuptake inhibition, validating our design approach.

Topics: Dopamine; Dose-Response Relationship, Drug; Drug Design; Humans; Molecular Docking Simulation; Molecular Structure; Neurotransmitter Uptake Inhibitors; Norepinephrine; Piperidines; Serotonin; Structure-Activity Relationship; Tetrazoles

A series of multitarget directed propargylamines, as well as other differently susbstituted piperidines have been screened as potential modulators of neuronal nicotinic acetylcholine receptors (nAChRs). Most of them showed antagonist actions on α7 nAChRs. Especially, compounds 13, 26, and 38 displayed submicromolar IC50 values on homomeric α7 nAChRs, whereas they were less effective on heteromeric α3β4 and α4β2 nAChRs (up to 20-fold higher IC50 values in the case of 13). Antagonism was concentration dependent and noncompetitive, suggesting that these compounds behave as negative allosteric modulators of nAChRs. Upon the study of a series of less complex derivatives, the N-benzylpiperidine motif, common to these compounds, was found to be the main pharmacophoric group. Thus, 2-(1-benzylpiperidin-4-yl)-ethylamine (48) showed an inhibitory potency comparable to the one of the previous compounds and also a clear preference for α7 nAChRs. In a neuroblastoma cell line, representative compounds 13 and 48 also inhibited, in a concentration-dependent manner, cytosolic Ca(2+) signals mediated by nAChRs. Finally, compounds 38 and 13 inhibited 5-HT3A serotonin receptors whereas they had no effect on α1 glycine receptors. Given the multifactorial nature of many pathologies in which nAChRs are involved, these piperidine antagonists could have a therapeutic potential in cases where cholinergic activity has to be negatively modulated.

Topics: Acetylcholine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Calcium; Cell Line, Tumor; Dose-Response Relationship, Drug; Inhibitory Concentration 50; Isoxazoles; Membrane Potentials; Microinjections; Neuroblastoma; Nicotinic Agonists; Nicotinic Antagonists; Oocytes; Patch-Clamp Techniques; Phenylurea Compounds; Piperidines; Receptors, Nicotinic; Receptors, Serotonin, 5-HT3; Serotonin; Xenopus laevis

Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer's disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic - NBP (8), caffeic - NBP (9), and ferulic - DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic - NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro.

Topics: Alzheimer Disease; Amines; Animals; Antioxidants; Cell Line, Tumor; Cholinesterases; Drug Design; Humans; Male; Mice; Molecular Targeted Therapy; Monoamine Oxidase; Neuroprotective Agents; Piperidines

Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds show effective AchE inhibitions, high selectivities over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of quinolone derivatives to serve in the design of N-benzylpiperidine linked multipotent molecules for the treatment of Alzheimer Disease has been established.

Topics: Acetylcholinesterase; Alzheimer Disease; Antioxidants; Binding Sites; Catalytic Domain; Cholinesterase Inhibitors; Humans; Molecular Docking Simulation; Piperidines; Quinolones; Structure-Activity Relationship

Several hH3R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. Nevertheless, many promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity and their dibasic character. Analysis of previously, as potential PET ligands synthesized compounds (ST-889, ST-928) revealed promising results concerning physicochemical properties and drug-likeness. Herein, the synthesis, the evaluation of the binding properties at the hH3R and the estimation of different physicochemical and drug-likeness properties of further novel benzylpiperidine variations on H3R antagonists is described. Due to the introduction of various small hydrophilic moieties in the structure, drug-likeness parameters have been improved. For instance, compound 12 (ST-1032) showed in addition to high affinity at the H3R (pKi (hH3R)=9.3) clogS, clogP, LE, LipE, and LELP values of -2.48, 2.18, 0.44, 7.14, and 4.95, respectively. Also, the keto derivative 5 (ST-1703, pKi (hH3R)=8.6) revealed LipE and LELP values of 5.25 and 6.84, respectively.

Topics: Histamine Antagonists; Humans; Kinetics; Ligands; Piperidines; Protein Binding; Receptors, Histamine H3

Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The screening results showed that most of compounds exhibited potent anti-AChE activity in the range of nM concentrations. Among them, compound 10c bearing an N-ethylcarboxamide linker and a 6-nitro substituent showed the most potent activity (IC₅₀ = 0.3 nM) and the highest selectivity (SI = 26,300). Compound 10c was 46-fold more potent than standard drug donepezil against AChE. The kinetic study revealed that compound 10c exhibited mixed-type inhibition against AChE. Protein-ligand docking study demonstrated that the target compounds have dual binding site interaction mode and these results are in agreement with kinetic study.

Topics: Acetylcholinesterase; Amides; Animals; Butyrylcholinesterase; Cholinesterase Inhibitors; Coumarins; Dose-Response Relationship, Drug; Electrophorus; Horses; Models, Molecular; Molecular Structure; Piperidines; Structure-Activity Relationship

The synthesis, biological assessment and molecular modeling of new pyridonepezils1-8, able to inhibit human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE), are described. The new compounds have been designed as hybrids resulting from a conjunctive approach that combines the N-benzylpiperidine moiety, present in donepezil, and the 2-amino-6-chloropyridine heterocyclic ring system, connected by an appropriate polymethylene linker. Compounds 1-8 were prepared by reaction of 2-amino-6-chloro-4-phenylpyridine-3,5-dicarbonitrile (13) [or 2-amino-6-chloropyridine-3,5-dicarbonitrile (14)] with 2-(1-benzylpiperidin-4-yl)alkylamines (9-12). The biological evaluation of molecules 1-8 showed that compounds 1-6 are potent AChE inhibitors, in the submicromolar, while compounds 7 and 8 are on the nanomolar range, the most potent, 2-amino-6-((3-(1-benzylpiperidin-4-yl)propyl)amino)pyridine-3,5-dicarbonitrile (7), showing a IC(50) (hAChE) = 9.4 ± 0.4 nM. Inhibitors 2-8 are permeable as determined in the PAMPA assay. Compared to donepezil, compound 7 is in the same range of inhibitory activity for hAChE, and 703-fold more selective for hAChE than for hBuChE. Molecular modeling investigation on pyridonepezil7 supports its dual AChE inhibitory profile, binding simultaneously at the catalytic active and at peripheral anionic sites of the enzyme. The theoretical ADME analysis of pyridonepezils1-8 has been carried out. Overall, compound 7, a potent and selective dual AChEI, can be considered as a candidate with potential impact for further pharmacological development in Alzheimer's therapy.

Topics: Acetylcholinesterase; Alzheimer Disease; Aminopyridines; Binding Sites; Blood-Brain Barrier; Butyrylcholinesterase; Cholinesterase Inhibitors; Donepezil; Enzyme Assays; Humans; Indans; Models, Biological; Models, Molecular; Nitriles; Permeability; Piperidines; Protein Binding; Pyridines; Structure-Activity Relationship

An ion-neutral complex (INC)-mediated hydride transfer reaction was observed in the fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in electrospray ionization mass spectrometry. Upon protonation at the nitrogen atom, these compounds initially dissociated to an INC consisting of [RC(6)H(4)CH(2)](+) (R = substituent) and piperidine or piperazine. Although this INC was unstable, it did exist and was supported by both experiments and density functional theory (DFT) calculations. In the subsequent fragmentation, hydride transfer from the neutral partner to the cation species competed with the direct separation. The distribution of the two corresponding product ions was found to depend on the stabilization energy of this INC, and it was also approved by the study of substituent effects. For monosubstituted N-benzylpiperidines, strong electron-donating substituents favored the formation of [RC(6)H(4)CH(2)](+), whereas strong electron-withdrawing substituents favored the competing hydride transfer reaction leading to a loss of toluene. The logarithmic values of the abundance ratios of the two ions were well correlated with the nature of the substituents, or rather, the stabilization energy of this INC.

Topics: Cycloheptanes; Piperazines; Piperidines; Protons; Spectrometry, Mass, Electrospray Ionization; Thermodynamics; Toluene

The study presents synthesis and biological activity of novel alkyl- and arylcarbamate derivatives with N-benzylpiperidine and N-benzylpiperazine moieties designed as cholinesterases inhibitors. These fragments turned out to determine compounds' selectivity between AChE and BuChE. Derivatives of N-benzylpiperazine (16-25) were selective BuChE inhibitors with 3-(2-(4-benzylpiperazin-1-yl)-2-oxoethyl)-phenyl butylcarbamate (22) being the most potent compound (pIC50=5.00) while a series of carbamate derivatives of N-benzylpiperidine (5-14) displayed non-selective BuChE/AChE inhibitory activity. Molecular modelling studies point out significant differences between orientations of these two groups of compounds in the active site of AChE, which can be an explanation of their different biological activity.

Topics: Acetylcholinesterase; Butyrylcholinesterase; Carbamates; Cholinesterase Inhibitors; Enzyme Activation; Kinetics; Models, Molecular; Molecular Structure; Piperazines; Piperidines; Stereoisomerism; Structure-Activity Relationship

Monoamine releasers constitute one class of drugs currently under investigation as potential agonist medications for the treatment of cocaine dependence. The efficacy and safety of monoamine releasers as candidate medications may be influenced in part by their relative potency to release dopamine and serotonin, and we reported previously that releasers with approximately 30-fold selectivity for dopamine versus serotonin release may be especially promising. The present study examined the effects of the releasers benzylpiperazine, (+)phenmetrazine, and 4-benzylpiperidine, which have 20- to 48-fold selectivity in vitro for releasing dopamine versus serotonin. In an assay of cocaine discrimination, rhesus monkeys were trained to discriminate 0.4 mg/kg i.m. cocaine from saline in a two-key, food-reinforced procedure. Each of the releasers produced a dose- and time-dependent substitution for cocaine. 4-Benzylpiperidine had the most rapid onset and shortest duration of action. Phenmetrazine and benzylpiperazine had slower onsets and longer durations of action. In an assay of cocaine self-administration, rhesus monkeys were trained to respond for cocaine injections and food pellets under a second order schedule. Treatment for 7 days with each of the releasers produced a dose-dependent and selective reduction in self-administration of cocaine (0.01 mg/kg/injection). The most selective effects were produced by phenmetrazine. Phenmetrazine also produced a downward shift in the cocaine self-administration dose effect curve, virtually eliminating responding maintained by a 30-fold range of cocaine doses (0.0032-0.1 mg/kg/injection) while having only small and transient effects on food-maintained responding. These findings support the potential utility of dopamine-selective releasers as candidate treatments for cocaine dependence.

Topics: Animals; Biogenic Monoamines; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Conditioning, Operant; Discrimination, Psychological; Dopamine; Dopamine Uptake Inhibitors; Food; Macaca mulatta; Male; Norepinephrine; Phenmetrazine; Piperazines; Piperidines; Reward; Serotonin; Synaptosomes

1-Benzylpiperazine (also known as 'Legal X', 'Legal E', or 'A2') is a psychoactive compound increasingly encountered on the clandestine market. Previous experimental data suggest that the compound possesses addictive properties. In the present study, we used the conditioned place preference method in the rat to test whether 1-benzylpiperazine possesses rewarding properties. Furthermore, the mechanisms of the 1-benzylpiperazine reward were investigated using selected dopamine and serotonin receptor antagonists. 1-Benzylpiperazine (1.25, 5, and 20 mg/kg) induced dose-dependently place preference. This place preference was attenuated by the antagonists SCH23390 (0.2 mg/kg; dopamine D1-like receptors) and MDL72222 (1.0 mg/kg; serotonin3 receptors), but not by raclopride (0.8 mg/kg; dopamine D2-like receptors) or ketanserin (2 mg/kg; preferentially serotonin2 receptors). Our results show that 1-benzylpiperazine possesses rewarding properties in the rat, which suggests the compound to be susceptible to human abuse. The brain dopaminergic and serotonergic systems appear to be involved in the 1-benzylpiperazine reward.

Topics: Animals; Behavior, Animal; Benzazepines; Conditioning, Psychological; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Ketanserin; Male; Piperidines; Psychotropic Drugs; Raclopride; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Serotonin, 5-HT2; Receptors, Serotonin, 5-HT3; Reward; Serotonin 5-HT2 Receptor Antagonists; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Substance-Related Disorders; Tropanes

A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzylpiperidine fragment has been synthesised. The acetylcholinesterase (AChE) inhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 13 was as active as tacrine in reversing the blockade induced by tubocurarine at rat neuromuscular junction. Additionally, receptor binding studies provided new lead compounds for further development of alpha2-adrenergic and sigma-receptor antagonists. Molecular dynamic simulation using X-ray crystal structure of AChE from Torpedo californica was used to explain the possible binding mode of these new compounds.

Topics: Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Male; Models, Molecular; Neuromuscular Blocking Agents; Piperidines; Rats; Rats, Sprague-Dawley; Thiadiazines

Automated docking and three-dimensional Quantitative Structure-Activity Relationship studies (3D QSAR) were performed for a series of 82 reversible, competitive and selective acetylcholinesterase (AChE) inhibitors. The suggested automated docking technique, making use of constraints taken from experimental crystallographic data, allowed to dock all the 82 substituted N-benzylpiperidines to the crystal structure of mouse AChE, because of short computational times. A 3D QSAR model was then established using the CoMFA method. In contrast to conventional CoMFA studies, the compounds were not fitted to a reference molecule but taken in their 'natural' alignment obtained by the docking study. The established and validated CoMFA model was then applied to another series of 29 N-benzylpiperidine derivatives whose AChE inhibitory activity data were measured under different experimental conditions. A good correlation between predicted and experimental activity data shows that the model can be extended to AChE inhibitory activity data measured on another acetylcholinesterase and/or at different incubation times and pH level.

Topics: Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Mice; Models, Molecular; Piperidines; Protein Binding; Static Electricity; Structure-Activity Relationship

A series of 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives and of N-benzylpiperidine benzisoxazoles has been investigated using the comparative molecular field analysis (CoMFA) approach. These compounds have been found to inhibit the metabolic breakdown of the neurotransmitter acetylcholine (ACh) by the enzyme acetylcholinesterase (AChE) and hence alleviate memory deficits in patients with Alzheimer's Disease by potentiating cholinergic transmission. Development of the CoMFA model considered two separate alignments: (i) alignment I which emphasized the electrostatic fitting of the subject compounds and (ii) alignment II which emphasized their steric fitting. In addition, the inhibitor compounds were considered both as neutral species and as N-piperidine-protonated species. The resulting 3D-QSAR indicates a strong correlation between the inhibitory activity of these N-benzylpiperidines and the steric and electronic factors which modulate their biochemical activity. A CoMFA model with considerable predictive ability was obtained.

Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Models, Molecular; Piperidines

Topics: Animals; Arteriosclerosis; Atherosclerosis; Piperidines; Rabbits

Topics: Amines; Female; Humans; Piperidines; Uterus

Topics: Amines; Benzylamines; Female; Humans; Oxytocics; Piperidines; Uterus