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PubMed1987

Doubtful role for phencyclidine metabolites in PCP enhancement of QNB binding.

In vivo administration of phencyclidine (PCP) has been shown to enhance the accumulation of intravenously administered 3H quinuclidinyl benzilate (QNB) in certain regions of mouse brain. Since this effect can be blocked by prior administration of atropine, it has been interpreted as an enhancement by PCP of the specific binding of QNB. The present studies replicated this earlier work and determined that two major hydroxy metabolites of PCP found in rodents 1-(1-phenylcyclohexyl)4-hydroxy piperidine (4-OH-pip PCP) and 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (4-OH-cyclo PCP) probably do not contribute substantially to the PCP effect on QNB binding. Though QNB accumulation in brain was increased by injection of 4-OH-cyclo PCP, the doses necessary for the effect were substantially higher than those needed for PCP. Furthermore, pretreatment of the animals with beta-diethylaminoethyl diphenylpropylacetate (SKF525A), a compound known to block the metabolism of PCP in liver microsomes and thus the formation (at least in part) of these metabolites, did not attentuate the PCP effect on QNB binding.

Animals↗
PubMed1987

Effect of phencyclidine and two monohydroxy metabolites on 3H QNB binding in vivo in rats.

The purpose of these investigations was to determine if phencyclidine (PCP) and/or two of its major monohydroxy metabolites [1-(1-phenylcyclohexyl)4-hydroxy piperidine (4-OH-pip PCP) and 1-(1-phenyl-4-hydroxycyclohexyl) piperidine (4-OH-cyclo PCP)] influence 3H quinuclidinyl benzilate (QNB) binding in rat brain after in vivo administration. PCP and 4-OH-pip PCP but not 4-OH-cyclo PCP enhanced QNB binding. The effect was blocked by atropine. Since the dose of 4-OH-pip PCP necessary to alter QNB binding in rat brain is substantially higher than that required for PCP, this metabolite probably does not play a major role in the PCP effect on QNB binding in rat brain.

Animals↗
PubMed1989

Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs.

Thirty-seven arylcyclohexylamines including phencyclidine (PCP) and derivatives, N[1-(2-thienyl)cyclohexyl]piperidine (TCP) and derivatives and N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) were assessed for their ability to inhibit [3H]PCP binding and [3H]dopamine ([3H]DA) synaptosomal uptake. Their pharmacological property (ataxia) was measured by means of the rotarod test. A very good correlation was observed between the inhibition of [3H]PCP binding and the [3H]DA uptake only for arylcyclohexylamines bearing an unmodified phenyl group. Conversely the comparison between the inhibition of [3H]PCP binding and the activity in the rotarod test shows a good correlation with arylcyclohexylamines having any aromatic group (phenyl, substituted phenyl and thienyl rings). This study outlined a new compound (BTCP) without ataxic effect, which is one of the more potent inhibitors of the [3H]DA uptake (IC50 = 8 nM) and which seems very specific since it has a low affinity for [3H]PCP receptors (IC50 = 6 microM). These data show that the aromatic group of the compounds leads to molecules that bind differently to the PCP receptor and to the DA uptake complex. They also suggest that the behavioral properties of arylcyclohexylamines revealed by the rotarod test occur essentially as a result of an interaction with the sites labeled with [3H]PCP and that TCP is more selective than PCP itself in this recognition.

Animals↗
PubMed1981

Haloperidol pharmacokinetics: a preliminary study in rhesus monkeys using a new radioimmunoassay procedure.

The development, validation, and application of a new radioimmunoassay for haloperidol in biological fluids is described. The antiserum, raised against N-amino-butyl chlorophenyl piperidine bovine albumin conjugate, could not distinguish between haloperidol and its reduced metabolite, but it could discriminate against chlorophenyl piperidine (cross-reaction 2.6%). The fluorophenyl metabolites of haloperidol were not recognized by the antiserum. Haloperidol determinations were made on less than 100 microliter aliquots of human and rhesus monkey plasma or diluted urine without prior extraction of the sample. The radioimmunoassay was applied to the study of the pharmacokinetics of intravenous haloperidol administration to two male rhesus monkeys. Salient features of the results are as follows. As with man, the plasma concentration versus time curve could be resolved into three compartments, but there were differences in the distribution of haloperidol between the compartments. The apparent volume of distribution for the two monkeys examined was 5.87 L kg-1 and 7.37 L kg-1, considerably smaller than in man, a difference almost entirely due to a much smaller tissue compartment. The biological half-life of 15.97 hr and 7.56 hr was similar to man. The mean hepatic extraction ratio was calculated to be 0.032 and 0.056, and the data suggested that hepatic metabolism of haloperidol may be of lesser importance in rhesus monkey than in man. An insignificant proportion (0.01%) of the administered dose was excreted as haloperidol in the urine.

Animals↗
PubMed1982

Mutagenicity of pyrolysates from guanidine, ureide, secondary amines and polyamines found by the Salmonella/mammalian-microsome test.

Nitrogenous compounds such as guanidine, ureide, secondary amines and polyamines were pyrolysed at 300, 400, 500 and 600 degrees C for 3 min, and the mutagenic activities of the pyrolysates were assayed on Salmonella typhimurium TA98 and TA100 with or without metabolic activation by S9 mix. Among 21 pyrolysates tested, 14, from methylguanidine, agmatine, dihydrouracil, dimethylamine, diethylamine, trimethylamine, triethylamine, pyrrolidine, morpholine, sarcosine, piperazine, piperidine, spermine and spermidine, showed mutagenic activity. In the presence of S9 mix, the mutagenic activity began to appear from the pyrolysate at 400 degrees C, and the pyrolysate at 600 degrees C showed the highest mutagenic activity except that from methylguanidine. The mutagenic activity formed by pyrolysis was more active on TA98 than TA100. In the absence of S9 mix, only 3 pyrolysates - from dimethylamine, diethylamine and pyrrolidine - showed slight mutagenic activity toward TA100. The highest mutagenic activity was observed with the pyrolysate from spermine, followed by those from piperidine, spermidine, piperazine and triethylamine. Some nitrogenous compounds showed slight mutagenic activity after pyrolysis at 300 degrees C for 20 min, although none of the compounds tested showed any mutagenic activity after pyrolysis at 300 degrees C for 3 min.

Amines↗
PubMed1988

Antibodies against haloperidol specific to the butyrophenone moiety.

Polyclonal and monoclonal antibodies to the D2-dopamine receptor antagonist haloperidol were produced by immunization with haloperidol conjugated to bovine serum albumin either through the tertiary hydroxy group of the piperidine ring (halo(OH)-BSA), or through the keto group of the butyrophenone (halo(CO)-BSA). Polyclonal rabbit antisera raised against halo(OH)-BSA exhibited high affinity for [3H]haloperidol. A fraction of these antibodies also bound [3H]spiperone with high affinity. Inhibition of the [3H]spiperone binding by various butyrophenone derivatives displayed a specificity similar to that observed for the inhibition of [3H]spiperone binding to the D2-dopamine receptor. Both monoclonal antibodies raised against halo(CO)-BSA(AG-58) and against halo(OH)-BSA(AC-91) exhibited high binding affinities to haloperidol. Monoclonal antibody AG-58 cross-reacted primarily with butyrophenone derivatives that are closely related to haloperidol in their substitutions on the piperidine ring. On the other hand, monoclonal antibody AC-91 cross-reacted with a wide range of butyrophenones with binding specificities resembling those of the dopamine receptor.

Animals↗
PubMed1988

DNA damage induced by ascorbate in the presence of Cu2+.

DNA damage induced by ascorbate in the presence of Cu2+ was investigated by use of bacteriophage phi X174 double-stranded supercoiled DNA and linear restriction fragments as substrates. Single-strand cleavage was induced when supercoiled DNA was incubated with 5 microM-10 mM ascorbate and 50 microM Cu2+ at 37 degrees C for 10 min. The induced DNA damage was analyzed by sequencing of fragments singly labeled at their 5'- or 3'-end. DNA was cleaved directly and almost uniformly at every nucleotide by ascorbate and Cu2+. Piperidine treatment after the reaction showed that ascorbate and Cu2+ induced another kind of DNA damage different from the direct cleavage. The damage proceeded to DNA cleavage by piperidine treatment and was sequence-specific rather than random. These results indicate that ascorbate induces two classes of DNA damage in the presence of Cu2+, one being direct strand cleavage, probably via damage to the DNA backbone, and the other being a base modification labile to alkali treatment. These two classes of DNA damage were inhibited by potassium iodide, catalase and metal chelaters, suggesting the involvement of radicals generated from ascorbate hydroperoxide.

Ascorbic Acid↗
PubMed1995

Methylene blue-mediated photooxidation of 7,8-dihydro-8-oxo-2'-deoxyguanosine.

One well known product of the methylene blue-mediated photosensitization of 2'-deoxyguanosine (dG) in oxygen saturated aqueous solution is 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG). We observed that the rate of 8-oxodG photodecomposition by methylene blue-mediated photosensitization is approx. 3-times faster than for dG. The primary products of the methylene blue-mediated photosensitization of 8-oxodG are 2-amino-5-((2-deoxy-beta-D-erythro-pentofuranosyl)amino)-4H-imidazol-4-o ne (dIz), 2,2-diamino-4-((2-deoxy-beta-D-erythro-pentofuranosyl)amino)-5(2H)-oxazo lone (dZ), the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine (dO), and an as yet unidentified product with a molecular weight of 287 (dX). Except for the latter product, these compounds have all been identified following the methylene blue-mediated photooxidation of dG. Methylene blue-mediated photooxidation of 8-oxodG in D2O instead of H2O leads to a 4-fold increase in the rate of 8-oxodG photodecomposition while the addition of sodium azide retards the reaction, observations which imply that the reaction occurs via a type II (singlet oxygen mediated) mechanism. Like 8-oxodG, dIz and dZ are sensitive to hot piperidine and likely contribute to strand breaks observed in double stranded DNA exposed to methylene blue plus light followed by hot piperidine. Because 8-oxodG generates predominately G-->T transversions, the photooxidation of 8-oxodG to dIz, dO, and dX may explain the predominance of G-->C transversions in single-stranded M13mp2 bacteriophage DNA exposed to methylene blue plus light and then transfected into SOS-induced Escherichia coli.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1985

Conformational and dynamic features of cocaine in DMSO-d6 solution.

13C spin-lattice relaxation rates, 13C {1H} NOESs, 1H spin-spin relaxation rates and 1H two-dimensional magnetization transfer spectroscopy were used for delineating conformational features of cocaine in DMSO-d6 solution. Two main conformations differing in the orientation of the plane made by the benzoxy substituent with respect to the piperidine ring principal axis were observed. Relatively slow interconversions of the piperidine ring were delineated together with the main motional features of the whole molecule.

Journal Article↗
PubMed1984

A physiologically active kainic acid-preferring receptor in chicken retina.

Neurotoxicity induced by intravitreal injections of kainic acid in the chicken retina was effectively antagonized by piperidine 2,3-dicarboxylic acid and to a lesser extent D-gamma-glutamylglycine. 2-Amino-5-phosphonovaleric acid and glutamic acid diethyl ester were much less effective antagonists. These effects probably result from interactions with a kainic acid-preferring receptor localized on the OFF-centre bipolar cells. Piperidine 2,3-dicarboxylic acid and D-gamma-glutamylglycine also blocked selectively the OFF-responses of ganglion cells while glutamic acid diethyl ester was without effect. 2-Amino-5-phosphonovaleric acid rapidly blocked ON and, much more slowly, OFF-responses. These results are consistent with a role for kainic acid-preferring receptors located on the OFF-centre bipolar cells in chicken retina in physiological transmission between photoreceptors and the OFF-centre bipolar cells.

2-Amino-5-phosphonovalerate↗
PubMed1990

Photoaffinity labeling and binding studies reveal the existence of two types of phencyclidine receptors in the NCB-20 cell line.

The mouse neuroblastoma-Chinese hamster brain hybrid cell line NCB-20 is the only clonal cell line in which binding studies indicate the presence of phencyclidine (PCP) receptor-like sites. We report here that polypeptide components of NCB-20 cell PCP sites were identified with the photolabile PCP derivative [3H]N-[1-(3-azidophenyl)cyclohexyl]piperidine ([3H]AZ-PCP). The pharmacological selectivity of [3H]AZ-PCP binding (under reversible conditions) was similar to that observed for [3H]N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding to NCB-20 cell membranes. Inhibition of [3H]TCP binding by AZ-PCP, dexoxadrol or MK-801 was biphasic, suggesting the presence of two types of PCP sites on NCB-20 cells. Photolysis of NCB-20 cell membranes pre-equilibrated with [3H]AZ-PCP, followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), revealed the presence of 5 major labeled bands (Mr 90,000, 68,000, 49,000, 40,000 and 33,000), a pattern similar to that observed for rat brain membranes. MK-801 and D-2-amino-5-phosphonovaleric acid (D-(-)-AP5) selectively inhibited the labeling of Mr 68,000 and 90,000 polypeptides. These results indicate that the labeled bands represent constituents of at least two different PCP binding proteins. The Mr 68,000 and 90,000 components appear to correspond to a high-affinity site, which comprises approximately 20% of total [3H]TCP sites in these cells, and exhibits the pharmacology expected for the PCP receptor of the N-methyl-D-aspartate (NMDA)-gated channel.

Animals↗
PubMed1986

An analysis of the effects of excitatory amino acid receptor antagonists on evoked field potentials in the olfactory bulb.

The effects of excitatory amino acid antagonists on extracellular field potentials in the olfactory bulb produced by lateral olfactory tract stimulation were analysed in vivo. The compounds tested D-2-amino-5-phosphonovalerate, L-(+)2-amino-4-phosphonobutyrate, gamma-D-glutamylglycine, L-glutamic acid diethylester and cis-2,3-piperidine dicarboxylic acid, were administered by brain dialysis. Of the compounds tested, only cis-2,3 piperidine-dicarboxylic acid and gamma-D-glutamylglycine were able to suppress the synaptic excitation of granule cells. This pharmacological profile suggests the involvement of non-N-methyl-D-aspartate receptors. However, the suppression was accompanied by a reduction in the amplitude of the presynaptic volley. A second finding was that D-2-amino-5-phosphono-valerate and gamma-D-glutamyl glycine attenuated granule cell mediated inhibition of mitral cells, suggesting the involvement of N-methyl-D-aspartate-sensitive receptors. The possibility that mitral cells and that either centrifugal fibres, or an intrinsic olfactory bulb feedback loop might use an excitatory amino acid as its neurotransmitter is therefore discussed.

2-Amino-5-phosphonovalerate↗
PubMed1989

Subchronic administration of MK-801 in the rat decreases cortical binding of [3H]D-AP5, suggesting down-regulation of the cortical N-methyl-D-aspartate receptors.

The effects of the subchronic administration of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine (MK-801) (0.5 mg/kg twice daily, 7 days) on N-methyl-D-aspartate, phencyclidine and sigma binding sites, behaviour and catecholamine turnover were investigated in the rat. Overt behaviours induced by MK-801 on day 7 were significantly altered relative to day 1 with subchronically treated rats not showing head weaving, goss ataxia or loss of hindlimb control: locomotion and sniffing were largely unaffected. The mean intensities of behaviour were 1.8 and 5.4 for days 7 and 1, respectively. Behavioural tolerance was accompanied by a significant reduction in the density of cortical N-methyl-D-aspartate receptors as measured by [3H]D-2-amino-5-phosphonopentanoic acid binding, while affinity was unchanged: the density of binding sites was 3.52 and 1.88 pmol/mg protein for saline- and MK-801-treated rats, respectively. The N-methyl-D-aspartate ion channel as measured by the binding of [3H]N-(1-[2-thienyl]cyclohexyl)piperidine was not affected by the schedule of MK-801. Additionally, changes were not observed to N-methyl-D-aspartate- or glycine-stimulated [3H]N-(1-[2-thienyl]cyclohexyl)piperidine binding or to sigma binding. Catecholamine turnover was unaltered in the nucleus accumbens septi after the schedule of MK-801. Our results demonstrate that the subchronic administration of MK-801 produces behavioural tolerance and down-regulation of N-methyl-D-aspartate binding sites and suggest differential regulation of the domains of the N-methyl-D-aspartate receptor-ionophore complex.

2-Amino-5-phosphonovalerate↗
PubMed1990

MK-801 pretreatment enhances N-methyl-D-aspartate-mediated brain injury and increases brain N-methyl-D-aspartate recognition site binding in rats.

Direct intracerebral administration of N-methyl-D-aspartate typically produces focal brain injury. (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-immi ne maleate (MK-801), a non-competitive N-methyl-D-aspartate antagonist, can protect against N-methyl-D-aspartate-mediated brain injury when administered shortly before or after an intracerebral injection of N-methyl-D-aspartate. However, in this study we report that in perinatal rats if MK-801 (1 mg/kg) is administered intraperitoneally 24 h prior to a unilateral intrastriatal N-methyl-D-aspartate injection, N-methyl-D-aspartate-mediated brain injury is paradoxically enhanced. The severity of resulting brain injury is 15-25% greater in groups that received MK-801 in comparison with saline-treated controls (P less than 0.001, linear regression analysis). In contrast, the severity of brain injury resulting from intrastriatal injection of the glutamate agonist quisqualate is not altered by a similar 24 h MK-801 pretreatment. Furthermore, the enhanced toxicity of N-methyl-D-aspartate produced by a 24 h pretreatment with MK-801 is completely blocked if a second dose of MK-801 is administered 15 min after the intrastriatal injection of N-methyl-D-aspartate. To determine if MK-801 produced alterations in glutamate receptor pharmacology co-incident with the enhanced toxicity of N-methyl-D-aspartate, in vitro quantitative autoradiography for excitatory amino acid receptor subtypes was performed with [3H]glutamate and [3H]N-1-(2-thienyl)cyclohexyl-3,4-piperidine in seven-day-old rats killed 2 or 24 h after MK-801 (1 mg/kg) administration. A 2 h MK-801 pretreatment produced a 30-50% increase in [3H]glutamate binding at N-methyl-D-aspartate preferring recognition sites in all four brain regions examined (areas CA1 and CA3 of the hippocampus, corpus striatum, cingulate cortex) in comparison with saline-treated controls (P less than 0.05, ANOVA). [3H]N-1-(2-Thienyl)cyclohexyl-3,4-piperidine binding to the phencyclidine site associated with the N-methyl-D-aspartate receptor was reduced by 60-80% in all brain regions examined (P less than 0.001). Quisqualate-sensitive [3H]glutamate binding was not altered by a 2 h MK-801 pretreatment. In animals that received a 24 h MK-801 pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Control of 40-Hz firing of reticular thalamic cells by neurotransmitters.

This study bears on the control exerted by neurotransmitters on the expression of a 40-Hz pacemaker activity observed in reticular thalamic cells. Experiments were conducted in urethane-anaesthetized rats using extracellular recordings and local applications of antagonists against the neurotransmitters involved in the modulation of reticular thalamic cells. All drugs were dissolved in a Ringer's solution (pH 7.4) and were applied in small quantities (25-150 nl) by pressure through one barrel of a micropipette assembly. Forty-Hertz firing was abolished by local application of the alpha 1 antagonist prazosin and by bilateral lesion of the locus coeruleus. Local applications of glutamate antagonists reduced the rate of discharges by 30-50% as did cortical cooling or complete transection of the internal capsule. Conversely, scopolamine exerted a permissive action on the expression of 40-Hz activities; many spontaneously bursting units started firing at 40 Hz under the influence of this muscarinic antagonist. Since reticular thalamic cells are GABAergic and synaptically coupled via axonal collaterals, we investigated how GABAergic drugs affected the regular firing of these cells. Local applications of bicuculline produced a transient increase of the firing rates while the application of GABA induced intermittent pauses on a background of regular discharges. The application of piperidine-4-sulphonic acid, a GABAA receptor agonist, produced a similar effect. The length of pauses generated by piperidine was statistically analysed. It was found that the duration of short pauses was a multiple integer of the mean interspike interval of surrounding discharges. The preservation of the period and phase of the rhythm across the pauses implies that a subthreshold oscillation was presented into the cells during the arrests of discharges. Given the mode of action of noradrenaline and acetylcholine on reticular thalamic neurons, and considering a possible metabotropic action of glutamate, the above results suggest that deactivation of a leaky K conductance is critically involved in the regular firing of these cells in urethane-anaesthetized rats. Alternatively, because reticular cells are coupled via inhibitory synapses, it is proposed that the 40-Hz firing frequency reflects, in the frequency domain, a point of equilibrium in the reticular thalamic network when the leaky K conductance is fully deactivated by the metabotropic effects of monoamines and/or excitatory amino acids.

2-Amino-5-phosphonovalerate↗
PubMed1986

Optimized conditions for solid-phase sequencing: simultaneous chemical cleavage of a series of long DNA fragments immobilized on CCS anion-exchange paper.

A solid-phase method for simultaneous sequencing of ten or more long DNA fragments has been developed, using as support the cellulose matrix for chemical sequencing (CCS), anion-exchange paper [Rosenthal et al., Nucl. Acids Res. 13 (1985) 1173-1184]. We optimized several of the seven steps which include: (i) immobilization; (ii) washing; (iii) modification; (iv) washing; (v) sorting of the paper segments; (vi) piperidine reaction and chemical elution, and (vii) lyophilization. During carrier-supported chemical cleavage with dimethylsulfate (DMS) (G), HCOOH (A + G), KMnO4 (T greater than Pu) and NH2OH (C), losses of immobilized DNA are very low. DNA fragments ranging in length from several hundred bp up to 6 kb can be effectively chemically eluted from CCS paper during the piperidine reaction with an efficiency of more than 90%. Because no DNA salt elution and ethanol precipitation steps are necessary the method is rapid, convenient and allows complete automation.

Anions↗
PubMed1988

Site-specific cleavage of single-stranded and double-stranded DNA sequences by oligodeoxyribonucleotides covalently linked to an intercalating agent and an EDTA-Fe chelate.

An oligodeoxythymidylate, oligo [d(T8)], was covalently linked to an acridine derivative via its 3' end and to EDTA via its 5' end. The octathymidylate was targeted to a single-stranded DNA fragment 27 nucleotides in length containing an octadeoxyadenylate sequence. In the presence of Fe(II) and a reducing agent (dithiothreitol) cleavage reactions were induced in the nucleotide sequence. The extent of the reaction was dependent on oligo concentration, salt concentration and temperature. Dissociation of the complexes at high temperature or low salt concentration abolished the site-specific cleavage reactions. Treatment of the reacted DNA with piperidine or piperidine-formiate strongly enhanced the yield of cleavage reactions demonstrating that damages were induced on nucleic acid bases by the EDTA-Fe complex covalently linked to the octathymidylate. At high salt concentration (1 M NaCl) or in the presence of spermine and ethylene-glycol a triple helix was formed involving the 27-mer DNA fragment and two oligo[d(T8)]. One of the oligo[d(T8)] was bound parallel and the other antiparallel to the oligo[d(A8)] complementary sequence. Cleavage reactions were induced on both sides of this oligo[d(A8)] target sequence. When a 27-mer duplex was used as a target the oligo[d(T8)] was bound in a parallel orientation with respect to the oligo[d(A8)]-containing strand in the major groove of the double helix. Cleavage reactions were induced on the oligo[d(A8)]-containing strand by the EDTA-Fe chelate attached to the 5' end of the oligo[d(T8)].

Acridines↗
PubMed1990

Synthesis of fluorine-18 labeled GABA uptake inhibitors.

The first syntheses of fluorine-18 labeled inhibitors of GABA reuptake [(R,S)-1-[2-[4-[18F]fluorophenyl]phenyl]methoxyethyl]piperidine- 3-carboxylic acid, (R,S)-1-[2-[(4-[18F]trifluoromethyl)phenyl][(4- trifluoromethyl)phenyl]-methoxyethyl]piperidine-3-carboxylic acid] are described. These N-substituted nipecotic acid derivatives were prepared in no-carrier-added form by the condensation of the appropriately substituted [18F]benzhydryl chlorides (prepared in three steps from [18F]fluoride ion) with N-(2-hydroxyethyl)nipecotic acid ethyl ester, followed by ester hydrolysis. Overall radiochemical yields were 17-28% (corrected, 150 min synthesis time). A simple new method for synthesis of a [18F]trifluoromethyl group by the nucleophilic substitution of a bromodifluoromethyl substituent has also been developed.

Fluorine Radioisotopes↗