Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PIPERIDINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1988

Cardiovascular effects of 1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride.

1-Methyl-4-(1-naphthylvinyl)piperidine (B-120) produced a dose related decrease in blood pressure in cats. B-120 did not alter the cardiovascular response to acetylcholine or vagal stimulation. It did not affect the response of the nictitating membrane to both pre- and post-ganglionic stimulation. In isolated cortical synaptosomes, B-120 decreased calcium flux below basal levels. Thus, the blockade of calcium channels appeared to be related to the production of hypotension and may be the mechanism by which B-120 protected against organophosphate toxicity.

Animals↗
PubMed1989

(+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine binding to sigma receptors in mouse brain in vivo.

Binding of i.v. administered (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H]3-PPP) in the brain of intact mice is antagonized dose responsively by sigma receptor ligands. The correlation of potencies for inhibition of binding in vivo and in vitro indicates that sigma receptors in mouse brain are labeled in vivo by i.v. [3H]3-PPP. 3-PPPP, the N-phenylpropyl derivative of norpropyl-3-PPP exhibits very high affinity for sigma receptors in vitro and in vivo.

Animals↗
PubMed1990

Multiple sites of action of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP) in blood vessels.

Functional effects of the sigma ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), were explored in perfused rat tail and rabbit ear arteries in vitro. In the rat tail artery (+)-3PPP inhibited contractile responses to adrenergic nerve stimulation, an effect which was reversed to potentiation by the dopamine D2 receptor antagonist sulpiride. In the rabbit ear artery, however, (+)-3PPP potentiated contractile responses to nerve stimulation, an effect which was unchanged by sulpiride. In the rat tail artery, blockade of norepinephrine uptake by cocaine and deoxycorticosterone in the presence of sulpiride revealed two additional actions of (+)-3PPP. First, an inhibitory action on the monoamine uptake site was confirmed by direct measurement of [3H]norepinephrine accumulation. Second, at higher concentrations, an action to inhibit contractile responses to adrenergic nerve stimulation was manifested at a still unidentified site. These studies demonstrate that the observed functional effect of (+)-3PPP results from its combined actions on three individual sites with the net effect dependent on the relative densities of these different receptor sites in each type of vessel.

Animals↗
PubMed1984

The hypothermic effect of 4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl (CGP 6085 A) in Wistar Kyoto rats.

CGP 6085 A [4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl], a reported serotonin uptake and MAO (16) inhibitor, is a potent hypothermic agent. The hypothermic action of CGP 6085 A is dose dependent with a maximal reduction in rectal core temperature of greater than 1 degree C within one hour after drug administration. Fluoxetine and citalopram elicit a similar response at equal doses. These results suggest that inhibition of serotonin uptake may produce the hypothermic effect. To assess the in vivo action of CGP 6085 A in inhibiting hypothalamic serotonin uptake, CGP 6085 A (10 mg/kg) was injected one hour prior to injection of 3-hydroxy-4-methyl-alpha-ethyl-phenylethylamine (H75/12), a serotonin depletor. The ability of CGP 6085 A to block the uptake of H75/12 by the 5HT uptake system was indicative of its ability to block serotonin uptake. Pretreatment with p-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, resulted in the loss of the hypothermic response to CGP 6085 A. Thus, these data are consistent with the idea that CGP 6085 A may produce its hypothermic response by inhibiting serotonin uptake.

Amphetamines↗
PubMed1986

(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] but not (-)-3-PPP produces (+)-N-allylnormetazocine-like (SKF 10,047) discriminative stimuli.

In rats trained to discriminate the prototypic sigma receptor agonist, (+)-N-Allylnormetazocine [(+)-N-Allylnormetazocine [(+)-NANM/SKF 10,047], from saline, the (+)- but not the (-)-isomer of 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) produced (+)-NANM-like discriminative stimuli. (+)-3-PPP binds stereo selectively to the (+)-NANM binding site, but not to the phencyclidine binding site. Additionally, phencyclidine was found to produce (+)-NANM-like discriminative stimuli. Although the 3-PPP isomers were shown to produce changes in central dopaminergic activity (Hjorth et al. Life Sci 37, 673, 1985), the discriminative stimulus properties of (+)-3-PPP are apparently not mediated via the dopaminergic system. This hypothesis is supported by the fact that apomorphine did not produce (+)-NANM-like discriminative stimuli. These stimuli are thus non-dopaminergic and may be due to the (+)-3-PPP actions at the sigma binding site. However, it is possible that (+)-NANM, PCP, and (+)-3-PPP may have common non-sigma pharmacologic properties that account for the similar discriminative stimulus properties of these compounds.

Animals↗
PubMed1990

Computer-assisted analysis of dextromethorphan and (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites in rat brain. Allosteric effects of ropizine.

Computer-assisted analysis of self- and cross-displacement studies between dextromethorphan (DM) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine ((+)-3-PPP) demonstrated in the rat brain the existence of two high-affinity and one low-affinity binding site for each ligand. One high-affinity site is the common DM1/sigma 1 site, the affinity of which is allosterically increased 4 to 5-fold by 10 microM ropizine. The Kd values of the DM1/sigma 1 for DM and (+)-3-PPP are 17 and 11 nM respectively. DM binds to the second high-affinity site (R2) with a Kd of 15 nM; this site has low affinity for (+)-3-PPP. Conversely, (+)-3-PPP binds with high affinity (Kd 53 nM) to another site (R3), that has low-affinity for DM. The Bmax of the common DM1/sigma 1 site in the rat is about ten times smaller than that in the guinea pig. Thus, extreme caution should be exercised in extrapolating from one species to another. Since DM and most sigma ligands bind to more than one site, not all of which are shared, it is important not to attribute the complex pharmacological effects of these ligands to a single hypothetical receptor.

Allosteric Site↗
PubMed1984

Modulation of the responses to the GABA-mimetics, THIP and piperidine-4-sulphonic acid, by agents which interact with benzodiazepine receptors. An electrophysiological study on cultured mouse neurones.

Electrophysiological recordings from mouse neurones in tissue culture have been used to investigate how agents which interact with the benzodiazepine receptor modulate neuronal responses to gamma-aminobutyric acid (GABA) and its mimetics, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and piperidine-4-sulphonic acid (P4S). Experiments were performed in a physiological medium, pH 7.35 at 34-36 degrees C. gamma-Aminobutyric acid, THIP and P4S were applied by iontophoresis to neuronal somata. Responses were assessed by current-clamp or voltage-clamp recordings. Midazolam (an agonist at the benzodiazepine receptor) and the beta-carboline, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM; an inverse agonist at the BZ receptor), were applied by pressure ejection from blunt pipettes. The potency order of the agonists was GABA greater than P4S greater than THIP. Midazolam (10(-7)-10(-5) M) potentiated responses to all three agonists to a similar extent with a shift to the left of the dose-response curve. The drug DMCM (10(-6)-10(-5) M) decreased the responses to all three agonists to a similar extent. The DMCM-induced depression was of a non-competitive nature. It has previously been proposed that THIP is a partial agonist and P4S an antagonist at the GABA receptor coupled to the benzodiazepine receptor, or that the benzodiazepine-receptor-coupled and electrophysiological GABA receptors are distinct. In the present study, responses to the three agonists were modulated to a comparable extent following manipulation of the benzodiazepine receptor. It is therefore unnecessary to invoke the above explanations to account for these results.

Animals↗
PubMed1991

(+) 3-[3-hydroxyphenyl-N-(1-propyl) piperidine] selectively differentiates effects of sigma ligands on neurochemical pathways modulated by sigma receptors: evidence for subtypes, in vivo.

The effects of sigma ligands, (+)3PPP 3-[3-hydroxyphenyl-N(1-propyl) piperidine] and (-)butaclamol, were evaluated in vivo on the metabolism of dopamine (DA) and in the striatum release of adrenocorticotrophic hormone (ACTH) and prolactin in the rat and changes in levels of cyclic guanosine monophosphate (cGMP) in the cerebellum of the mouse and compared with the effects of (+)NANM (N-allyl-normetazocine, SKF 10,047) and (+)pentazocine. Both (+)3PPP and (-) butaclamol decreased the release of prolactin and did not affect the metabolism of DA. N-Allyl-normetazocine and (+)pentazocine increased release of prolactin and have been shown previously to increase the metabolism of DA. All four ligands increased release of ACTH; however, only the increases caused by (+)NANM and (+)pentazocine were reversed by pretreatment with CPP, a N-methyl-D-aspartate (NMDA) receptor antagonist. (+)Pentazocine and (+)NANM inhibited the NMDA receptor-mediated changes in levels of cGMP in the cerebellum of the mouse, while (+)3PPP and (-)butaclamol did not attenuate the response to NMDA. In addition to further confirming a functional interaction between sigma receptors and NMDA receptors, these studies divide the observed effects of putative sigma ligands into two groups, characterized by benzomorphan compounds and non-benzomorphan compounds, suggesting the possibility of subtypes at sigma receptor in vivo.

Adrenocorticotropic Hormone↗
PubMed1986

Species differences in vacuolation of the choroid plexus induced by the piperidine-ring drug disobutamide in the rat, dog, and monkey.

A subchronic oral toxicity study of disobutamide, a piperidine ring compound with antiarrhythmic activity, was conducted at doses of 30, 100, and 250 mg/kg in rats, 45 mg/kg in dogs, and 90 mg/kg in monkeys. Numerous vacuoles were observed in various organs such as the liver, kidneys, heart, lungs, spleen, thymus, stomach, and choroid plexus in these animals. The epithelium of the choroid plexus (CP), however, showed severe vacuolation in rats and monkeys but not in dogs. The vacuoles corresponded to enlarged and myelin-figured lysosomes observed by electron microscopy, revealing morphological characteristics which have been reported as drug-induced phospholipidosis. In a further study, the drug penetration to cerebrospinal fluid (CSF) and the drug concentration in CP were examined in these animals. Daily po doses of 250, 45, and 90 mg/kg were, respectively, administered to rats, dogs, and monkeys to maintain approximate equivalency in peak blood concentrations across species, over a course of 35 days. The concentration of the drug in the CP was higher in rats and monkeys than in dogs, and the CSF/serum ratio of the drug concentration was extremely high in rats. The uptake of the drug by the CP in vitro was high in rats, monkeys, and dogs, in this order. In dogs, both direct contact of the drug with the CP during incubation and intraventricular administration induced vacuolation in the epithelium. From these results it was concluded that differences of the drug's penetration into the CSF and its uptake by the choroid plexus epithelium are responsible for the species differences of CP vacuolation in the animals.

Animals↗
PubMed1980

The effect of temperature and chloride ions on the stimulation of [3H]flunitrazepam binding by the muscimol analogues THIP and piperidine-4-sulfonic acid.

THIP and piperidine-4-sulfonic acid (PSA) interact with [3H]GABA binding sites and have GABAmimetic efficacy in vivo, but fail to enhance benzodiazepine receptor binding performed at 0 degree C. However, when [3H]flunitrazepam binding is determined at elevated temperature (30 or 37 degrees C), THIP and PSA display potent chloride ion-dependent stimulatory effects. These results resolve apparent discrepancies between the properties of GABA receptors observed in vivo and in vitro, and they suggest that the modulation of benzodiazepine receptor binding investigated at physiological temperatures can be used as an experimental system for the characterization of GABA receptors.

Animals↗
PubMed1996

N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and cocaine induce similar effects on striatal dopamine: a microdialysis study in freely moving rats.

N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and cocaine inhibit dopamine (DA) uptake but bind to different sites on the transporter. Their dose-dependent effects (i.p. administration) on extracellular DA levels in the rat striatum were measured by in vivo microdialysis. Both drugs dose-dependently increased DA levels with a maximum effect 60 min post injection. BTCP (20 mg/kg) had a greater peak effect than cocaine (40 mg/kg). For doses inducing similar behavioral effects (cocaine, 20mg/kg; BTCP, 10 mg/kg) similar DA increases were observed in the striatum and the nucleus accumbens. Although both drugs bind on the DA transporter on different sites and induce different behavioral effects when administered chronically, their acute administration increased striatal DA level in a similar way.

Animals↗
PubMed1986

Brain-stem areas tonically inhibiting dorsal horn neurones: studies with microinjection of the GABA analogue piperidine-4-sulphonic acid.

In barbiturate anaesthetized cats, tonic inhibition of the excitation of lumbar dorsal horn neurones by impulses in unmyelinated primary afferents was measured by reversibly cooling the spinal cord at the thoraco-lumbar junction. Tonic inhibition was reduced by microinjection of the GABA analogue, piperidine-4-sulphonic acid (2.5 nM in 0.5 microliter) mainly at AP -7, L 2-5 and V -8 to -10. This area in the ventrolateral medulla is just ventral to the facial nucleus and has been shown to be important in cardiovascular control, particularly in relation to fear-defence reactions. It is proposed that tonic inhibition of the nociceptive responses of spinal neurones is part of such a reaction in response to the trauma of surgery. Since previous experiments had shown that the ventrolateral medulla was important in spinal inhibition produced by PAG stimulation, these experiments support the proposal that analgesia does not occur in isolation but is part of a complex behavioural response of an animal in a potentially injurious environment.

Action Potentials↗
PubMed1995

3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine elicits convulsant effects in mice.

1. The behaviour and EEG effects of the dopamine and sigma (sigma) ligands (+) 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)3-PPP) were studied in mice. 2. (+) 3-PPP dose-dependently (60-100 mg/kg i.p.) produced behavioural and electrical tonic-clonic seizures. 3. The incidence of the tonic seizures elicited by 100 mg/kg of the drug was significantly (P < 0.05) prevented by spiperone (0.5 mg/kg i.p.) and haloperidol (0.5 mg/kg i.p.). 4. The results show an influence on the behavioural and electrical threshold of convulsions by (+) 3-PPP depending on a prevalent interference on dopamine receptors.

Animals↗
PubMed1990

Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse isolated hypogastric ganglion.

The actions of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)3-PPP] on sympathetic neurons of the mouse isolated hypogastric ganglion were studied using the current clamp and single electrode voltage clamp techniques. In neurons studied under current clamp (+)3-PPP (10(-5) to 3 x 10(-4) M) evoked a concentration-dependent depolarization, which was fully reversible on washout of the drug. The depolarization was associated with an increase in membrane input resistance. At membrane potentials between -43 and -65 mV the amplitude of the depolarization was inversely related to the membrane potential. (+)3-PPP had no effect on membrane potential at potentials negative to -65 mV. The effect of (+)3-PPP on the M-current was studied in cells voltage clamped at -40 mV and stepped to -60 mV for 300-500 ms. The slow current relaxations seen during and after the voltage step are largely due to the M-current. (+)3-PPP (3 x 10(-5) to 3 x 10(-4) M) inhibited the M-current and produced an inward current in a concentration-dependent manner. (-)3-PPP (3 x 10(-5) M) had similar effects, but was less potent than (+)3-PPP. (+)3-PPP (3 x 10(-5) M) also inhibited the A-current and a calcium-dependent potassium current, but to a lesser degree than the M-current.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Identification of lactams as in vitro metabolites of piperidine-type phenothiazine antipsychotic drugs.

The metabolism of the piperidine-type phenothiazine antipsychotic agents thioridazine, mesoridazine and sulforidazine was studied in vitro with 10,000 g liver supernatants obtained from rats and dogs. After incubations at 37 degrees C for different time intervals, the incubates were extracted with dichloromethane and the isolated compounds analyzed by HPLC, direct probe MS and on-line HPLC-MS. Five lactam metabolites of these three drugs were unequivocally identified in the rat in vitro system, but none was found in dog preparations; at least one lactam metabolite was identified for each drug in the rat. The lactams of thioridazine and thioridazine ring sulfoxide were characterized as metabolites of thioridazine for the first time in any system. The other three lactam metabolites, namely the lactams of mesoridazine, sulforidazine and mesoridazine ring sulfoxide, were found in vitro for the first time, although they have been previously reported as in vivo metabolites of these drugs. The results indicate that rat would be a more suitable animal model than dog for further studies on the formation of lactam metabolites of these drugs.

Animals↗
PubMed1995

Structure-activity relationship studies of CNS agents--XVII. Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] as a probe defining the extended topographic model of 5-HT1A receptors.

Spiro[piperidine-4',1-(1,2,3,4-tetrahydro-beta-carboline)] (10), its derivatives 11-15 and its analogs 16 and 17 were examined as ligands of serotonin 5-HT1A receptors. It was shown that compounds 12 and 14 had essentially the same 5-HT1A affinity as 1-phenylpiperazine and its rigid analog 7, whereas there were substantial differences in the steric arrangement of their crucial pharmacophores, i.e. aromatic and protonation centers. On the basis of the existing models and using the (+)-LSD structure as a template, a new, extended three-point topographic model of 5-HT1A receptors has been proposed.

Animals↗
PubMed1995

Amides of piperidine, morpholine and piperazine substituted 1-phenylethylamines: inhibitors of acylCoA:cholesterol acyltransferase (ACAT) activity in vitro and in vivo.

Amides of some substituted 1,2-diarylethylamines have been shown to exhibit potent acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) inhibitory activity in vitro in microsomal ACAT assays but show poor in vivo activity in a cholesterol-fed hamster model. In an effort to design ACAT inhibitors that are potent in both our in vitro and in vivo assays a series of amides of piperidine, morpholine and piperazine substituted 1-phenylethylamines were synthesized. Compounds of this series were found to be very potent inhibitors of ACAT in a microsomal ACAT assay and also exhibited potent activity in a cholesterol-fed hamster model.

Amides↗
PubMed2004

Synthesis, radiosynthesis and in vivo evaluation in mice of [123I]-(4-fluorophenyl) {1-[2-(4-iodophenyl)ethyl]piperidin-4-yl}methanone for visualization of the 5-HT2A receptor with SPECT.

This work reports the synthesis, radiolabelling and preliminary in vivo evaluation of [(123)I]-(4-fluorophenyl){1-[2-(4-iodophenyl)ethyl]piperidin-4-yl}methanone. The tributylstannylprecursor was synthesized with a yield of 30%. Radiolabelling was performed using an electrophilic iododestannylation. Tracer yield was 80%, radiochemical purity was >95% and specific activity was at least 55 Ci/micromol. Log P was 1.5. The tracer showed uptake in mice brain (2.72% ID/g tissue at 5 min p.i.) and therefore will be evaluated further by regional brain biodistribution and displacement studies in rabbits.

Animals↗