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At least 1,441 records · Page 80Linked to original sources
PubMed1992

Characterization of specific binding sites for [3H]-1,3-di-o-tolyl-guanidine (DTG) in the rat glioma cell line C6-BU-1.

The aim of the present study was to find out if a cell line of glial origin possesses sigma and/or phencyclidine (PCP) binding sites. Binding of [3H]1,3-di-o-tolyl-guanidine (DTG), a highly selective ligand for sigma binding sites, and of [3H]N-[1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP), a radioligand specific for PCP receptors, to C6-BU-1 glioma cells was investigated. Binding of [3H]DTG to C6-BU-1 cell membranes was reversible, saturable (Bmax = 10.5 pmol/mg protein), and of high affinity (KD = 26 nM). C6-BU-1 cells do not possess PCP receptors as indicated by negligible specific binding of [3H]TCP to C6-BU-1 cell membranes. Specific binding of [3H]DTG was reduced in the presence of Ca2+ and to a lesser extent by Mg2+. The rank order of potency of various PCP and sigma ligands was DTG > (+)3-[(3-hydroxy-phenyl)-N-n-propyl-piperidine] [(+)3-PPP] > haloperidol > pentazocine > (-)3-PPP > PCP > metaphit > dextromethorphan > (-)butaclamol > (+)butaclamol > (-)N-allylnormetazocine [(-)SKF 10,047] > MK801 > (+)SKF 10,047 > ketamine. The drug specificity, confirmed by a reversed stereoselectivity for the benzomorphan opiate SKF 10,047, indicated that these sites correspond to a subtype of sigma binding sites, the so-called sigma 2 binding site. Thus, the C6-BU-1 cell line is the first glial cell line demonstrated to have sigma 2 binding sites.

Animals↗
PubMed1990

In vivo labeling of phencyclidine (PCP) receptors with 3H-TCP in the mouse brain.

The phencyclidine (PCP) derivative N-[1-(2-thienyl)cyclohexyl]-piperidine (3H-TCP) was used to label in vivo the N-methyl-D-aspartate (NMDA) receptor-associated ionic channel in the mouse brain. After the injection of a tracer dose of 3H-TCP, a spread labeling throughout the brain was observed, but was the highest in the cerebellum. Preadministration of unlabeled TCP (30 mg/kg) resulted in a 90% reduction of 3H-TCP binding. PCP, TCP, MK-801, dexoxadrol, ketamine, and SKF 10,047 isomers dose-dependently prevented the in vivo 3H-TCP binding. ID50 determined in the cerebrum and the cerebellum were respectively correlated with K0.5 for 3H TCP high (rat cortex) and low affinity (rat cerebellum) sites in vitro. The pharmacological specificity of the 3H-TCP binding site in the cerebellum was significantly different from that in the cerebrum. ID50 values were generally higher than in the cerebrum and, particularly, MK-801, the most potent drug in the cerebrum, was without significant effect in the cerebellum, at any time and at doses as high as 30 mg/kg. N-[1-(2-benzo(b) thiophenyl)cyclohexyl]piperidine (BTCP), desipramine, and atropine showed a more efficient prevention of 3H-TCP binding in the cerebellum than in the cerebrum. The prevention of the binding by TCP or PCP, at doses close to their ID50 values, was rapid and then decreased slowly. The effect of MK-801 was long-lasting. This study confirm previous in vitro studies: 3H-TCP is an efficient tool for the labeling of the NMDA receptor-associated ionic channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Inhibition of the ATP-sensitive potassium channel in the guinea pig substantia nigra by BMS 181100 is not mediated by a sigma-binding site.

Quantitative autoradiography of brain tissue has revealed a high density of binding sites for the K-ATP channel antagonists, the sulphonylureas, and for sigma-ligands in the substantia nigra (SN). In view of the high density of the two binding sites in the SN the possibility has been investigated that the K-ATP channel and the sigma-binding site are functionally linked. The K-ATP channel-mediated membrane hyperpolarisation and decrease in input resistance produced by hypoxia and by the metabolic inhibitor, cyanide, in rostral substantia nigra pars compacta neurons are antagonised by the sigma-ligand BMS 181100. In addition, BMS 181100 antagonises activation of the K-ATP channel by diazoxide; cromakalim is found to be without effect in these neurons. Antagonism of the cyanide-induced hyperpolarisation is dose dependent and is observed at concentrations of the drug which have no observable effect on the resting membrane properties of the neurons. By contrast, the nonselective sigma ligands 1,3-di-O-tolylguanidine (10 microM) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (100 microM), and the selective sigma 1-ligand (+)-pentazocine (5-10 microM) have no effect on the cyanide-induced hyperpolarisation. 5-HT (50-100 microM) and the selective 5-HT1A receptor agonist 8-OH-DPAT (50 microM) also fail to antagonise the cyanide-induced hyperpolarisation. The antagonism of the cyanide-induced hyperpolarisation by BMS 181100 persists in the presence of tetrodotoxin (1 microM) and in the presence of high concentrations of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, but not under conditions of reduced calcium (0.1-0.2 mM) and raised magnesium (6 mM) concentrations, which block synaptic transmission. It is concluded that in substantia nigra phasic neurons the sigma-binding site does not regulate activation of the ATP-sensitive channel. However, BMS 181100 antagonises K-ATP channel activation in these neurons independently of sigma-binding sites and 5-HT receptors. This action of BMS 181100 is TTX insensitive and Ca2+ dependent.

Adenosine Triphosphate↗
PubMed1981

Quantification of phencyclidine in mainstream smoke and identification of phenylcyclohex-1-ene as pyrolysis product.

Parsley cigarettes containing [3H]phencyclidine were machine smoked, and the mainstream smoke was trapped in glass wool filters. Radioactivity was extracted from these filters with chloroform. The average recoveries of radioactivity were 76, 85, 70, and 69% for cigarettes containing 3, 10, 30, and 50 mg of [3H]phencyclidine hydrochloride, respectively. TLC and GLC-mass spectrometry were employed to identify and quantify compounds in the filter extracts. Approximately one-half of the recovered radioactivity represented a pyrolysis product, phenylcyclohex-1-ene. Formation of this product involved loss of piperidine from phencyclidine. Piperidine, which was not radiolabeled, also may appear in smoke intact. The remainder of the radiolabeled material represented unchanged phencyclidine. Therefore, the percentage of [3H]phencyclidine delivered was approximately 40% of the amount smoked. This result was independent of puff frequency and quantity of phencyclidine hydrochloride smoked over the range tested. The [3H]phencyclidine delivery was compared to the quantities of [3H]-delta 9-tetrahydrocannabinol and [3H]nicotine delivered in mainstream smoke. The recovery of unchanged [3H]-delta 9-tetrahydrocannabinol from placebo marijuana cigarettes injected with a solution containing 3 mg of delta 9-tetrahydrocannabinol was 60%. Tobacco cigarettes injected with [3H]nicotine yielded 70% unchanged nicotine in mainstream smoke.

Cannabis↗
PubMed1991

Synthesis and structural, conformational, and pharmacological study of some of esters derived from 3-phenethyl-3-azabicyclo[3.2.1]octan-8-beta-ol and the corresponding N-endo-methyl quaternary derivatives.

A series of 8-beta-acyloxy-3-phenethyl-3-azabicyclo[3.2.1]octane and its N-endo methiodides were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 8-beta-p-chlorobenzoyloxy-3-phenethyl-3-azabicyclo[3.2.1]octane methiodide (2c) was determined by X-ray diffraction. In CDCl3 solution, 1b-1e display the same preferred conformation. The cyclopentane and piperidine rings adopt an envelope conformation flattened at C-8 and a distorted chair conformation puckered at C-8 and flattened at N-3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. In all cases, methylation takes place from the endo position. The ability of the title compounds to antagonize the acetylcholine-induced contraction of guinea pig ileum is also reported. An initial structure-activity relationship is proposed.

Animals↗
PubMed1993

Synthesis and structural, biochemical, and pharmacological study of 3 beta-acyloxy-3 alpha-methoxycarbonyltropane derivatives.

A series of 3 beta-acyloxy-3 alpha-methoxycarbonyltropanes were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 3 alpha-methoxycarbonyl-3 beta-pyridincarbonyloxytropane (5d) was determined by X-ray diffraction. In CDCl3 solution, compounds 5a-f display the same preferred conformation. The pyrrolidine and piperidine rings adopt an envelope conformation flattened at N-8 and a distorted chair conformation puckered at N-8 and flattened at C3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. The pharmacological profile of one of these compounds makes it an adequate candidate for the design of novel GABAB antagonist agents.

Animals↗
PubMed1995

Synthesis and structural, conformational, biochemical, and pharmacological study of new compounds derived from tropane-3-spiro-4'(5')-imidazoline as potential 5-HT3 receptor antagonists.

A series of tropane-3-spiro-4'(5')-imidazolines was synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 2'-(1H-indol-3-yl)tropane-3-spiro-4'(5')-imidazoline hydrochloride 5(6)f was determined by X-ray diffraction. In CD3OD solution, compounds 5(6)a-f display the same preferred conformation. The pyrrolidine and piperidine rings adopt an envelope conformation flattened at N8 and a distorted chair conformation puckered at N8 and flattened at C3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. This conformation is similar to that observed for compound 5(6)f in the solid state. From binding studies on the compounds synthesized, compound 5(6)d demonstrated the ability to efficiently displace the binding of [3H]GR65630 to bovine brain area postrema membranes to an extent comparable to MDL 72222. In the von Bezold-Jarisch reflex, compound 5(6)d was equipotent with metoclopramide. It is, therefore, likely that the imidazoline ring may provide a useful bioisosteric replacement for the carbonyl group in 5-HT3 antagonists.

Animals↗
PubMed2002

Release of nitric oxide from novel diazeniumdiolates monitored by laser magnetic resonance spectroscopy.

We describe a technique in which for the first time laser magnetic resonance spectroscopy (LMRS) is used online to monitor the release of nitric oxide from synthetic NO donors. LMRS is a spectroscopic method for selective, sensitive (to 1 ppb), and time-resolved NO gas detection in the far-infrared and midinfrared spectral regions. We used two partly novel sets of diazeniumdiolates, the first set derived from N,N-diethylamine (-->DEA-NO), piperidine ((-->PIPE-NO), 2-methylpiperidine (-->MEPIPE-NO), and 2-ethylpiperidine (-->EPIPE-NO) and the second set derived from 2-, 3-, and 4-piperidine carboxylic acids (-->PIPECO-NO, NIPECO-NO, ISONIPECO-NO). We monitored the acid-catalyzed NO liberation from these compounds as influenced by parameters such as pH, temperature, concentration, and molecular structure. PIPECO-NO turned out to be the fastest donor of the group. The 3- and 4-substituted isomer derivatives were only negligibly faster releasers than unsubstituted PIPE-NO, which on the other hand showed to be faster than the higher homologues MEPIPE-NO and EPIPE-NO. The results demonstrate that varying neighboring groups affect the functional diazeniumdiolate group differently. A vicinal carboxyl group increases and alkyl groups decrease the rate of NO release.

Azo Compounds↗
PubMed1988

Discriminative properties of phencyclidine in mice: generalization to ketamine and monohydroxy metabolites.

The discriminative properties of phencyclidine (PCP) and their generalization to the effects of ketamine and monohydroxylated PCP metabolites were examined in C57BL/6cr mice utilizing two-lever operant procedures. As previously reported for pigeons and rats, PCP was discriminable in this species at a training dose of 3.0 mg/kg. PCP discriminability generalized to test doses of the drug that did not influence response rates (as low as 1.75 mg/kg) and also to ketamine (10 mg/kg). Both PCP monohydroxylated metabolites were active in mice. PCP partially generalized to the monohydroxylated metabolite, 1-(1-phenylcyclohexyl)4-hydroxy piperidine (PCHP) but not to 1-(1-phenyl-4-hydroxycyclohexyl) piperidine (PPC), which is consistent with previous reports on rats. The generalization of the PCP stimulus to PCHP was not as extensive in mice as previously reported for rats, suggesting that it may be less potent in this species. Although PCP discriminability generalized to PCHP, this generalization required PCHP doses that would produce tissue concentrations much higher than could result from discriminable doses of PCP. Therefore, the PCHP metabolite does not appear to mediate PCP discriminability in C57BL/6cr mice.

Animals↗
PubMed1982

Oral self-administration of phencyclidine analogs by rhesus monkeys: conditioned taste and visual reinforcers.

Three monkeys self-administered orally-delivered phencyclidine, 1-(1-phencyclohexyl) piperidine (PCP), N-ethyl-1-phencyclohexylamine (PCE), and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) over a wide range of concentrations (0.0156, 0.0312, 0.0625, 0.125, 0.25, and 0.5 mg/ml). Water was also available under a concurrent fixed-ratio (FR) 16 schedule. Drug deliveries were substantially higher than concurrent water deliveries at all concentrations, indicating that the three compounds functioned as effective reinforcers. Maximum liquid deliveries occurred at concentrations of 0.0625 (PCP and TCP) and 0.125 mg/ml (PCE). TCP was much shorter-acting (10-15 min) than PCP (4-6h) based on observations of severe ataxia at high concentrations. To investigate the conditioned reinforcing effects of taste, a quinine solution (0.088 mg/ml) was substituted for PCP (0.25 mg/ml) in five monkeys. Four monkeys responded for quinine in excess of water for a range of seven to over 30 sessions, while one monkey (M-R) did not show any substantial responding for quinine. With the same five monkeys (treatment order mixed), the effect of visual stimuli was tested by substituting water for PCP while retaining the visual stimuli indicating drug availability. Four monkeys showed increased responding on the side signaling drug for only 0-4 sessions, while one monkey (M-R) showed persistent responding for water on the side with drug stimuli for 29 sessions. These results indicated that taste functioned as an effective conditioned reinforcer, while visual stimuli appeared to be less effective in the oral drug self-administration paradigm.

Administration, Oral↗
PubMed1985

Phencyclidine increases the affinity of dihydropyridine calcium channel antagonist binding in rat brain.

Phencyclidine (PCP) significantly reduces the apparent dissociation constant (KD) of the dihydropyridine (DHP) calcium channel antagonist, [3H]nitrendipine, in synaptosomal membranes of rat and mouse brain without significantly effecting the maximum binding capacity (Bmax). At an optimum concentration of PCP (10 microM) the apparent KD of [3H]nitrendipine was reduced from 178 +/- 9 pM to 112 +/- 9 pM in rat forebrain, a 58% increase in affinity. The structural derivatives of PCP, P-Br-PCP [1-[1-(4-bromo-phenyl-cyclohexyl)piperidine]], m-NH2-PCP [1-[1-(3-anilo)-cyclohexyl]piperidine], (+/-)-PCMP [1-(1-phenyl)-cyclo-hexyl-3-methylpiperidine] also increased the apparent affinity of [3H]nitrendipine in the following order, p-Br-PCP much greater than PCMP greater than PCP greater than m-NH2-PCP. Local anesthetics either reduced the apparent affinity of [3H]nitrendipine or had no effect. Kinetic analysis revealed that PCP both increased the microassociation rate constant and decreased the microdissociation rate constant of [3H]nitrendipine. The magnitude of this enhanced binding varied with the brain region studied; the greatest increase in apparent affinity of [3H]nitrendipine was observed in striatum, while no significant increase in affinity was observed in brainstem. In some brain areas, PCP was more effective in reducing the KD in crude homogenates than in washed tissue. PCP (10 microM) did not alter the KD of [3H]nitrendipine to rat cardiac tissue. Both Ca2+ and Mg2+ inhibited the effect of PCP, while monovalent ions were ineffective in this regard.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Primary dissociated cultures of human brainstem cells: a useful tool for their characterization and neuroprotection study.

Dissociated cell cultures were prepared from brainstems of 5- to 10-week-old human fetuses. Catecholamine- as well as indolamine-containing cells were visualized using respectively dopamine (DA), noradrenaline (NA) and serotonin (5HT) as immunocytochemical markers. NA-, DA-, and 5HT-stained cells were characterized in the rhombencephalic cultures, representing respectively the fetal localization of the locus coeruleus and raphe nuclei. DA-stained cells were characterized in the mesencephalic cultures; these DA-cells originating from the substantia nigra presented morphological aspects different from the DA-rhombencephalic cells. Two types of GABA neurons and glial cells presenting glial fibrillary acidic protein (GFA-P) reactivity were also found in all the cultures. Two non-competitive N-methyl-D-aspartate antagonists, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) and cis-Pip/Me 1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine (GK11) in enantiomeric form (-), have been investigated for survival on rhombencephalic cultured cells. The number of 5HT-cells was found to be greater in the treated cultures than in the control ones. This in vitro system appears to be a useful tool for the investigation of the development of central nervous system (CNS) cells as well as the study of neuroprotection.

Brain Stem↗
PubMed1991

Effects of sigma receptor ligands on schedule-controlled behavior of rats: relation to sigma and PCP receptor binding affinity.

Eleven drugs were examined for their ability to inhibit sigma and phencyclidine (PCP) receptor binding, as labelled by (+)[3H]-R-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), [3H]ditolylguanidine (DTG), (+)[3H]N-allylnormetazocine (NANM) and [3H]1-(1-(2-thienyl)cyclohexyl)piperidine (TCP), in membrane preparations from whole rat brain. The same drugs were studied for their effects under a fixed-ratio (FR) schedule of food reinforcement in rats. The relative potency order of the drugs for decreasing FR responding was: haloperidol greater than (+)-3-PPP greater than (-)NANM greater than BMY 14802 greater than PCP greater than (+)NANM greater than DTG greater than rimcazole greater than JO 1783 greater than JO1784 greater than (-)butaclamol. The binding affinities of all 11 drugs for either the [3H]DTG, (+)[3H]-3-PPP, (+)[3H]NANM or [3H]TCP site did not correlate significantly with the potencies of the same drugs for decreasing FR behavior. Rimcazole, (+)-3-PPP and haloperidol, at behaviorally inactive doses, were studied for their effects as antagonists of the rate-decreasing effects of JO 1784, DTG and (+)NANM: rimcazole attenuated the effects of DTG and (+)NANM but not JO 1784; (+)-3-PPP attenuated the effects of (+)NANM but not JO 1784 and DTG; and haloperidol was devoid of antagonistic actions. Moreover, BMY 14802 did not attenuate the rate-decreasing effects of (+)-3-PPP. These results further indicate that it is difficult to distinguish between purported sigma agonist and antagonist drugs.

Animals↗
PubMed1992

Different capability of N-methyl-D-aspartate antagonists to elicit EEG and behavioural phencyclidine-like effects in rats.

Phencyclidine (PCP), a drug inducing schizophrenia-like symptoms in humans, is reported to be a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors. In rats, PCP produces three dose-dependent stages of EEG patterns: 1) increase of cortical desynchronization duration; 2) increase of the amplitude of the high-frequency (20-30 Hz) low-voltage (30-50 microV) cortical background activity; 3) appearance of cortical slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive effects such as stereotypy (circling, head weaving) and ataxia. In the present study, the EEG and behavioural effects induced by systemic administration of the NMDA antagonists dizocilpine (MK 801), dextromethorphan (DM), [(+)-alpha-(4-chlorophenyl)-4- [(phenyl)methyl-1-piperidine ethanol] (SL 82.0715), (+)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) have been compared to those of PCP in rats. The rank of potency for inducing PCP-like EEG stages 1-3 was as follows: MK 801 > PCP > CGS 19755 > CPP. These drugs also induced PCP-like behavioural effects. On the contrary, DM and SL 82.0715, administered up to the dose of 100 mg/kg IP, failed to induce PCP-like behavioural effects and elicited only the stage 1 of PCP-like EEG. These results strongly suggest the involvement of NMDA neurotransmission in the behavioral and EEG effects of PCP.

Analysis of Variance↗
PubMed1993

Elimination of plasmid pKM101 from Salmonella typhimurium by monoammonium salts.

The frequency of elimination of plasmid pKM101 from Salmonella typhimurium TA92 exposed to the action of 1-alkyl-1-ethylpiperidinium bromides and N-alkyl-N-[5-(benzoyloxy)-3-oxapentyl]-N,N-dimethylammonium bromides was non-linear in the homologous series. Change in the length of the alkyl chain markedly affected the elimination properties of the piperidine derivatives but had no effect on the elimination of benzoyl derivatives. Piperidines exhibited a weaker elimination capacity than the benzoyl derivatives. The most potent eliminator was the octylbenzoyl derivative, which causes the elimination of the plasmid in 80-85% cells.

Bromides↗
PubMed1997

NNC-19-1228 and NNC 22-0031, novel neuroleptics with a "mesolimbic-selective" behavioral profile.

NNC 19-1228 [1-(3(6-methylenedioxyphenylcarbamoyloxy) propyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl) piperidine] and NNC 22-0031 [4-(6-fluoro-1,2-benzisoxazol-3-yl) -1-(3-(3,4-methylenedioxyphenylcarbamoyloxy) propyl)piperidine] are newly developed compounds with an in vitro pharmacologic profile similar to that of clozapine, i.e., mixed dopamine (DA), 5-hydroxytryptamine (5-HT)2 and alpha 1-adrenergic antagonist action. In pharmacological experiments in mice, the compounds inhibited DA D2 receptor binding in vivo at doses that produced only moderate antagonism of methylphenidate (MPD)-induced stereotyped gnawing. However, the compounds were markedly more potent in blocking MPD-induced motility, a model which showed a high degree of sensitivity to alpha 1-adrenergic antagonism, but not 5-HT2 antagonism. In rats, the NNC-compounds blocked conditioned avoidance responding and attenuated the discriminative stimulus effects of amphetamine, but failed to induce catalepsy. These results are discussed in terms of adrenergic, serotonergic and dopaminergic interactions which suggest that the NNC compounds may act as DA antagonists with mesolimbic selectivity, and thus may have efficacy as antipsychotics without coincident extrapyramidal side effects.

Amphetamine↗
PubMed1987

Reduction and destruction rates of nitroxide spin probes.

A series of nitroxides was tested for rates of one-electron reduction in a chemical, a photochemical, and two biological systems by ESR assays. In all cases, piperidine and hydropyridine nitroxides were reduced consistently more rapidly than pyrroline and pyrrolidine nitroxides. Substituents on the nitroxides also affected reduction rates, although not as greatly as ring structure. One of the reduction systems, consisting of the photosensitizer FMN and the photoreductant EDTA, was used to study both anaerobic reduction and O2-dependent reoxidation of some of the nitroxides. Reduced piperidine and hydropyridine nitroxides were also oxidized more rapidly than the reduced pyrroline and pyrrolidine nitroxides. Reoxidation subsequent to reduction was partially inhibited by superoxide dismutase, indicating that superoxide radicals are involved in the process. Even after prolonged reoxidation, not all of the probe molecules were returned to their oxidized form, implying an irreversible "destruction" of the spin probe concomitant with its chemical reduction. Probe destruction was studied more specifically with a photochemical system for generating methyl radicals, which showed that these carbon-centered radicals destroyed different nitroxides at rates which were much less influenced by the nitroxide structures than one-electron reduction was.

Animals↗
PubMed1989

Exchange and shuttling of electrons by nitroxide spin labels.

The ability of nitroxide spin labels to act as oxidizers of reduced nitroxides (hydroxylamines) in biological and model systems was demonstrated. All of the nitroxides tested were able to act as oxidizing agents with respect to hydroxylamine derivatives of nitroxides. The rates of these reactions were first order with respect to nitroxide concentration and with respect to hydroxylamine concentration, making the reaction second order overall. The second-order rate constants are reported for a number of these reactions. These reactions proceeded to an equilibrium state and the equilibrium constants for several combinations of reactants are presented. Both the rate constants and the equilibrium constants were found to be dependent on the ring structure of the nitroxide and hydroxylamine, with piperidines being reduced more easily and pyrrolidines and oxazolidines being oxidized more easily. All of the hydroxylamine derivatives were oxidized by air to their respective nitroxides, with the rate of this oxidation greater for pyrrolidines than for piperidines. Furthermore, hydroxylamines that are permeable to lipid bilayers were able to act as shuttles of reducing equivalents to liposome-encapsulated nitroxides that were otherwise inaccessible to reducing agents. This mechanism of shuttling of electrons was able to explain the relatively rapid reduction by cells of a nonpermeable nitroxide in the presence of a permeable nitroxide.

Animals↗