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J L Neumeyer

Publications and source records attributed to J L Neumeyer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Use of high affinity, radioiodinated probes for identification of imidazoline/guanidinium receptive sites.

Various pharmacologically active compounds with an imidazoline or guanidinium moiety are recognized by membrane bound proteins that appear structurally and functionally distinct from known hormone receptors. Such entities are termed imidazoline binding sites, I receptors, or imidazoline/guanidinium receptive sites (IGRS). To facilitate the identification and structural analysis of IGRS, we developed functionalized molecular probes exhibiting high affinity and selectivity for IGRS. The molecular probes are structurally related to cirazoline, and imidazoline that exhibits high affinity for IGRS in both central and peripheral tissues. The parent molecule 2-[3-aminophenoxy]methyl imidazoline (125I-AMIPI), which was used to identify IGRS in brain and peripheral tissues. 125I-AMIPI was converted to the photosensitive arylazide derivative (125I-AMIPI) and used to identify the M(r) of the ligand binding subunit of IGRS in various tissues including brain, pancreas, kidney, and liver. The results of these studies indicate that there are multiple binding proteins for these molecules that differ in their apparent molecular weight, tissue distribution, intratissue location, and ligand recognition properties.

Animals↗
PubMed1995

Comparison of iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane for imaging of the dopamine transporter in the living human brain.

Several cocaine congeners are of potential for imaging the dopamine transporter (DAT). Previous studies have shown that iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) is a promising radiotracer for imaging the serotonin (5-HT) and dopamine (DA) transporters in the living human brain with single-photon emission tomography (SPET). [123I] beta-CIT was found to be not very practical for 1-day DAT imaging protocols since peak DAT uptake occurs later than 8 h. Here we report a pilot comparison of [123I] beta-CIT and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ([123I] beta-CIT-FP), using SPET imaging in four healthy male subjects. Peak uptake of [123I] beta-CIT-FP into the basal ganglia occurred earlier (3-4 h after injection of tracer) than that of [123I] beta-CIT (> 8 h). However, the specific DAT binding of [123I] beta-CIT-FP in the basal ganglia was somewhat less (0.813 +/- 0.047) than that of [123I] beta-CIT (0.922 +/- 0.004). Imaging quality is excellent with both tracers and they are potentially of value for brain imaging in various neuropsychiatric disorders.

Brain↗
PubMed1995

Iodine-123 labelled N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane for dopamine transporter imaging in the living human brain.

There are several cocaine analogs which have potential for imaging the dopamine transporters (DAT). Earlier studies have shown that iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT) and N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane ([123I]beta-CIT-FP) are promising DAT imaging agents in the living human brain with single-photon emission tomography (SPET). Here we report a pilot comparison of [123I]beta-CIT and [123I]beta-CIT-FP with a new tropane derivative, [123I]N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane ([123I]beta-CIT-FE), using SPET imaging in four healthy male subjects. Peak uptake of [123I]beta-CIT-FE into the basal ganglia occurred very rapidly (0.5 h after injection of tracer), after which the striatal washout obeyed a bi-exponential form. The specific DAT binding of [123I]beta-CIT-FE into the basal ganglia was somewhat less (0.785 +/- 0.117) than that of [123I]beta-CIT (0.922 +/- 0.004) or [123I]beta-CIT-FP (0.813 +/- 0.047). All these tracers have excellent imaging quality in healthy control subjects. However, the relatively fast washout of [123I]beta-CIT-FE and low temporal resolution of older SPET cameras may limit the use of this tracer to the measurement of the DAT density.

Adult↗
PubMed1995

Regional brain uptake and pharmacokinetics of [123I]N-omega-fluoroalkyl-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane esters in baboons.

Four N-omega-fluoroalkyl-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane ester (beta-CIT-FE), N-fluoropropyl, methyl ester (beta-CIT-FP), N-fluoroethyl, isopropyl ester (IP-beta-CIT-FE), and N-fluoropropyl, isopropyl ester (IP-beta-CIT-FP)] were labeled with 125I and evaluated in baboons by dynamic SPECT regional brain imaging, measurement of pharmacokinetics in arterial plasma, and whole body imaging. The labeled tracers were prepared by iododestannylation of the corresponding 4-(trimethylstannyl)phenyl compounds in radiochemical yield 63-96% and radiochemical purity > 96%. Regional SPECT brain imaging was carried out over a period of 5 h with a Strichman 810X Brain Imager to assess regional uptake in the striatum and midbrain compared to reference regions in the occipital cortex and cerebellum; arterial blood samples were taken for analysis of metabolites by solvent extraction and HPLC. The methyl esters showed higher total and specific peak uptake in the striatum than the isopropyl esters. Midbrain uptake was uniformly lower than striatal uptake and washed out more rapidly. beta-CIT-FE had more rapid striatal kinetics than beta-CIT-FP, with specific striatal washout rates of 10-14 vs 4-6% peak/h. Biodistribution of [123I] beta-CIT-FE and [123I] beta-CIT-FP measured by whole body conjugate imaging demonstrated major uptake in the brain, liver, and GI tract, with excretion occurring through both the renal and hepatobiliary routes. Absorbed radiation does estimates based on the MIRD schema indicated highest dose rates to the urinary bladder wall and lower large intestine wall (0.7 and 0.6 rad/mCi for [123I] beta-CIT-FE and 0.7 and 0.9 rad/mCi for [123I]beta-CIT-FP, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[O-methyl-11C]beta-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: preparation, autoradiography, metabolite studies, and positron emission tomography examinations.

beta-CIT-FP [N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-11C]beta-CIT-FP ([11C]beta-CIT-FP) was prepared by O-alkylation of the free acid with [11C]methyl iodide. The total radiochemical yield of [11C]beta-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was > 99%, and the specific radioactivity at time of injection was about 37 GBq/mumol (1000 Ci/mmol). Autoradiographic examination of [11C]beta-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [11C]beta-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of beta-CIT, indicating that striatal radioactivity following injection of [11C]beta-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [11C]beta-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [11C]beta-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

Animals↗
PubMed1995

Structural and ligand recognition properties of imidazoline binding proteins in tissues of rat and rabbit.

Imidazoline/guanidinium receptive sites (IGRS) belong to a family of membrane proteins that selectively recognize certain pharmacologically active compounds with an imidazoline or a guanidinium moiety. The role of such proteins in the cellular responses elicited by these compounds is unclear, but two members of this protein family are identical to isoforms of monoamine oxidase, an enzyme involved in the metabolism of monamine neurotransmitters. To characterize the structural and ligand recognition properties of the imidazoline binding proteins, we used the photoaffinity adduct [125I]iodoazidophe-noxymethylimidazoline ([125I]AZIPI) to label their ligand binding subunits in selected target tissues (kidney, pancreatic B cells, liver, and salivary gland). Photoaffinity labeling of membrane preparations or subcellular particulate fractions from various rat, rabbit, or hamster tissues indicated two labeled peptides of M(r) approximately 55,000 and approximately 61,000, the relative tissue distribution of which mirrored the expression of the A or B isoforms of monoamine oxidase. The ligand binding subunit of imidazoline binding proteins was identified on two peptides of M(r) approximately 55,000 and approximately 61,000 in rat and rabbit kidney, rat liver, rabbit salivary gland, and the pancreatic B cell line RIN-5AH, whereas only an M(r) approximately 61,000 peptide was observed in rat salivary gland and the hamster pancreatic B cell line HIT-T15. Saturation labeling experiments indicated that [125I]AZIPI exhibited similar affinity (Kd approximately 2-3 nM) for both the M(r) approximately 55,000 and approximately 61,000 peptides. However, competitive inhibition of photolabeling indicated that the two peptides were distinguished by their affinity for the guanidinium guanabenz or their interaction with potassium. Although some types of imidazoline binding sites are located on the enzyme monoamine oxidase, the nonisoform selective enzyme inhibitor pargyline did not alter photoaffinity labeling of either the M(r) approximately 55,000 or approximately 61,000 peptide, indicating that imidazolines/guanidiniums and active site inhibitors of monoamine oxidase interact with different domains on the enzyme. In rat kidney and liver, an additional photolabeled peptide of M(r) approximately 25,000 was observed, and its ligand recognition profile was distinct from the M(r) approximately 55,000 and approximately 61,000 species. In contrast with the mitochondrial location of the larger peptides, subcellular fractionation of liver homogenates indicated that the M(r) approximately 25,000 localized to the plasma membrane.

Affinity Labels↗
PubMed1995

Simplified multidose preparation of iodine-123-beta-CIT: a marker for dopamine transporters.

UNLABELLED: Iodine-123-beta-CIT is a SPECT radioligand for dopamine and 5-HT transporters with potential use in Parkinson's disease, schizophrenia and cocaine addiction studies. At present, preparation of no-carrier-added (NCA) [123I] beta-CIT is achieved by iododestannylation of a trialkylstannyl precursor with sodium [123I]iodide in the presence of oxidizing agent, followed by preparative HPLC. The purpose of this study was to develop a faster and simpler method for the routine preparation of this radiopharmaceutical. METHODS: Purification of the labeled compound was accomplished by solid phase extraction (SPE) with a C-18 Sep-Pak Light cartridge, which removed unreacted iodide, reaction reagents, polar side products and tributylstannyl precursor. The tributylstannyl precursor was preferred as starting material over the trimethylstannyl precursor due to its higher lipophilicity, allowing better separation of the labeled product and precursor. A TLC method was developed to assess the radiochemical purity of the final product. RESULTS: The method produced [123I] beta-CIT in high radiochemical yields (75% +/- 4%), with high radiochemical purity (> or = 98%) and specific activity (> 67000 Ci/mmole), in 1.5 hr. The final formulation was sterile and pyrogen free. CONCLUSION: The results obtained by solid phase extraction are consistent with those obtained by the HPLC method; with the advantage that the SPE method does not require solvent extraction, evaporation under reduced pressure or HPLC purification.

Binding Sites↗
PubMed1994

Effects of aporphine isomers on rat prolactin.

S(+)-aporphines are partial agonists at D2 dopamine receptors. High selectivity of anti-dopaminergic action in limbic vs. extrapyr amidal regions of rat brain and lack of induction of dopaminergic supersensitivity have suggested their potential as atypical antipsychotic drugs. Now, in testing for effects on circulating prolactin, a typical D2 antagonist haloperidol elevated, and potent agonist R(-)-11-hydroxy-N-propylnoraporphine lowered, serum prolactin levels in gentled male rats, while S(+)-N-propylnorapomorphine and its 11-monohydroxy analog had little or no effect, even at high doses. Lack of hyperprolactinemia adds to characteristics of S(+)-aporphines that are desirable in improved antipsychotics.

Animals↗
PubMed1994

Receptor affinities of aporphine enantiomers in rat brain tissue.

R(-) and S(+) enantiomers of apomorphine, N-n-propylnorapomorphine and 11-hydroxy-N-n-propylnorapomorphine were screened for affinity at over 40 representative sites in rat brain tissue that included amine, purine, amino acid and peptide receptors, transporters, ion channels, and effector components; only dopamine receptors and alpha-adrenoceptors showed appreciable affinity that was quantified further. The aporphines showed R(-) > S(+) isomeric selectivity as well as D2 > D1 selectivity at dopamine receptors. While R(-) isomers preferred alpha 2-adrenoceptors, S(+)-aporphines were alpha 1-selective, with similar affinity at alpha 1-adrenoceptors and dopamine D2 receptors. Interactions of S(+)-aporphines at alpha 1-adrenoceptors as well as dopamine D2 receptors may contribute to their unusual behavioral properties.

Animals↗
PubMed1994

Further characterization of [3H]ifenprodil binding in rat brain.

The present study was undertaken to characterize [3H]ifenprodil binding in rat brain. [3H]Ifenprodil showed saturable, high-affinity binding at 4 degrees C. Specific binding, defined with 10 microM ifenprodil as a competitor, was inhibited biphasically by the s receptor ligands, GBR 12909, 1,3-di-o-tolylguanidine (DTG), and (+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP). At 4 degrees C, 3 microM GBR 12909, which inhibited about 50% of specific binding of [3H]ifenprodil was used to mask sigma receptors. Under these conditions, specific binding of [3H]ifenprodil was inhibited potently by ifenprodil, SL 82.0715, poly(L-arginine), poly(L-lysine), neomycin, ruthenium red, spermine, arcaine and spermidine. In the presence of 3 microM GBR 12909, Zn2+ and Mg2+ partially inhibited specific binding of [3H]ifenprodil at 4 degrees C. In contrast, in the absence of GBR 12909, at 37 degrees C specific binding of [3H]ifenprodil was partially inhibited by Zn2+, but not by Mg2+. The anatomical distribution of [3H]ifenprodil binding at 4 degrees C (GBR 12909 included) in rat brain closely paralleled that of [3H]MK-801 (dizocilpine) binding (r = 0.971, P < 0.005). Without GBR 12909, specific [3H]ifenprodil binding at 37 degrees C was inhibited potently by sigma ligands. In the presence of 3 microM GBR 12909, [3H]ifenprodil binding at 4 degrees C was highest in synaptosomal and myelin fractions; however, without GBR 12909, [3H]ifenprodil binding at 37 degrees C was highest in microsomal and myelin fractions, consistent with the subcellular distribution of sigma receptors. The results suggest that, in the presence of 3 microM GBR 12909, at 4 degrees C, [3H]ifenprodil binds to sites that are sensitive to polyamines and related compounds; and that without GBR 12909, at 37 degrees C, [3H]ifenprodil interacts with sigma receptors in rat brain.

Adrenergic alpha-Antagonists↗
PubMed1994

S-(+)-aporphines are not selective for human D3 dopamine receptors.

1. Our aim was to test the hypothesis that selectivity for D3 dopamine (DA) receptors may contribute to limbic anti-DA selectivity of S-(+)-aporphine DA partial agonists. 2. Affinity was tested with 3H-emonapride, using human D3 receptors in mouse fibroblasts and D2 receptors in rat striatal tissue. 3. D3 receptors showed a picomolar affinity for 3H-emonapride, Na+ dependence, and reversible saturability, as well as stereoselectivity. Confirmatory or novel D3/D2 pharmacologic selectivity was found with several benzamides, thioxanthenes, buspirone, GBR-12909, and DA agonists including hydroxyaminotetralins [ADTN, (+)-7-OH-DPAT, (-)-PPHT and its fluorescein derivative], (-)-N-propylnorapomorphine, (-)-3-PPP, (-)-quinpirole, and SDZ-205-502, but neither aminoergoline nor (+)-aporphine partial agonists. 4. The results extend pharmacologic characterization of D3-transfected cell membranes but fail to account for the high limbic anti-DA selectivity of S-(+)-aporphines.

Animals↗
PubMed1994

Graphical, kinetic, and equilibrium analyses of in vivo [123I] beta-CIT binding to dopamine transporters in healthy human subjects.

The in vivo kinetics of the dopamine (DA) transporter probe 123I-labeled 2 beta-carboxymethoxy-3 beta-(4-iodophenyl) tropane ([123I] beta-CIT) in striatum was investigated with single-photon emission computerized tomography (SPECT) in five healthy human subjects. The aim of this study was to derive an adequate measure of the DA transporter density that would not be affected by regional cerebral blood flow or peripheral clearance of the tracer. SPECT data were acquired on the day of injection (day 1) from 0 to 7 h and on the following day (day 2) from 19 to 25 h. Arterial sampling on day 1 was used to measure the input function. Graphical, kinetic, and equilibrium analyses were evaluated. Graphical analysis of day 1 data, with the assumption of negligible dissociation of the tracer-receptor complex (k4 = 0), was found to be blood flow-dependent. A three-compartment kinetic analysis of day 1 data were performed using a three (k4 = 0)- and a four (k4 > 0)-parameter model. The three-parameter model estimated the konBmax product at 0.886 +/- 0.087 min-1. The four-parameter model gave a binding potential (BP) of 476 ml g-1, a value consistent with in vitro measurements. The stability of the regional uptake on day 2 allowed direct measurement of the specific to nonspecific equilibrium partition coefficient (V3" = k3/k4 = 6.66 +/- 1.54). Results of day 1 kinetic analysis and day 2 equilibrium analysis were well correlated among subjects. Simulations indicated that the error associated with the day 2 equilibrium analysis was acceptable for plasma tracer terminal half-lives > 10 h. We propose the equilibrium analysis on day 2 as the method of choice for clinical studies since it does not require multiple scans or the measurement of the arterial plasma tracer concentrations.

Adult↗
PubMed1994

Methyl 3 beta-(4-[125I]iodophenyl)tropane-2 beta-carboxylate in vitro binding to dopamine and serotonin transporters under "physiological" conditions.

Methyl 3 beta-(4-[125I]iodophenyl)tropane-2 beta-carboxylate ([123I]beta-CIT) is a single photon emission computed tomographic radiotracer for in vivo labeling of dopamine (DA) and serotonin (5-HT) transporters. Single photon emission computed tomographic experiments in nonhuman primates showed that [123I]beta-CIT in vivo binding to DA transporters had a much slower washout than binding to 5-HT transporters. This observation was not predicted from previously published in vitro studies. These studies, performed at 22 degrees C in nonphysiological buffer, reported similar affinity of [125I]beta-CIT for DA and 5-HT transporters. We now report [125I]beta-CIT binding parameters to fresh rat membranes at 22 degrees C and 37 degrees C, in a buffer mimicking the composition of cerebrospinal fluid. At both temperatures, binding to DA transporters was best fit by a two-site model, whereas binding to 5-HT transporters was compatible with one population of sites. At 22 degrees C, [125I]beta-CIT showed similar affinity to high-affinity DA (0.39 nM) and 5-HT transporter sites (0.47 nM). Increasing the incubation temperature from 22 degrees C to 37 degrees C reduced binding to DA transporters by 60%, whereas binding to 5-HT transporters was only marginally affected. In vitro kinetic experiments failed to detect significant differences in on or off rates that could explain the observed in vivo kinetics. These experiments thus failed to explain [125I]beta-CIT in vivo uptake kinetics, suggesting the existence of specific factors affecting the in vivo situation.

Animals↗
PubMed1994

Development of a high-affinity radioiodinated ligand for identification of imidazoline/guanidinium receptive sites (IGRS): intratissue distribution of IGRS in liver, forebrain, and kidney.

Imidazoline/guanidinium receptive sites (IGRS) are membrane proteins that exhibit high affinity for various compounds with an imidazoline or guanidinium moiety. The structure of these binding sites and their significance in the broad pharmacological action of such ligands are unclear. To address this issue, we developed selective high affinity compounds that could be radioiodinated and used as molecular probes for structural characterization of these proteins. This report describes the synthesis and characterization of such a molecule, 2-(3-amino-4-[125I]iodophenoxy)methylimidazoline ([125I]AMIPI). [125I]AMIPI is structurally related to cirazoline, an imidazoline exhibiting high affinity for IGRS and the family of related imidazoline binding sites. The phenyl-substituted analogue of cirazoline, 2-(3-aminophenoxy)methylimidazoline, was generated by alkylation of acetamidophenol with 2-chloromethylimidazoline. 2-(3-Aminophenoxy)methylimidazoline exhibited high affinity for IGRS in rabbit kidney membranes, as determined in competition binding studies with [3H]idazoxan (Ki = 12.5 +/- 7.5 nM), and was radioiodinated by chloramine-T oxidation to yield [125I]AMIPI. The binding properties of [125I]AMIPI were determined in membranes prepared from two representative tissues, rabbit kidney cortex and rat liver. Specific binding of [125I]AMIPI was saturable and of high affinity, as determined by Scatchard analysis of saturation binding isotherms (rabbit kidney, Kd = 2.0 +/- 0.9 nM, Bmax = 554 +/- 201 fmol/mg, five experiments; rat liver, Kd = 2.6 +/- 1.3 nM, Bmax = 73 +/- 10 fmol/mg, three experiments).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Whole-body biodistribution, radiation absorbed dose and brain SPECT imaging with iodine-123-beta-CIT in healthy human subjects.

UNLABELLED: SPECT imaging with 123I-labeled methyl 3 beta-(4-iodophenyl)tropane-2 beta-carboxylate ([123I]beta-CIT) in nonhuman primates has shown brain striatal activity, which primarily reflects binding to the dopamine transporter. The biodistribution and calculated radiation-absorbed doses of [123I]beta-CIT administered to eight healthy subjects were measured with attention to the accurate determination of organ time-activity data. METHODS: Whole-body transmission images were obtained with a scanning line source for attenuation correction of the emission images. Following administration of 92.5 +/- 22.2 MBq (2.5 +/- 0.6 mCi) of [123I]beta-CIT, subjects were imaged with a whole-body imager every 30 min for 3 hr, every 60 min for the next 3 hr and at 12, 24 and 48 hr postinjection. Regional body conjugate counts were converted to microcuries of activity, with a calibration factor determined in a separate experiment using a distributed source of 123I. RESULTS: The peak brain uptake represented 14% of the injected dose, with 2% of the activity approximately overlying the striatal region. Highest radiation-absorbed doses were to the lung (0.1 mGy/MBq, 0.38 rads/mCi), liver (0.087 mGy/MBq, 0.32 rads/mCi) and lower large intestine (0.053 mGy/MBq, 0.20 rads/mCi). CONCLUSIONS: Iodine-123-beta-CIT is a promising SPECT agent for imaging of the dopamine transporter in humans with favorable dosimetry and high brain uptake.

Adult↗
PubMed1993

Effect of trifluoromethyl and other substituents on activity of xanthines at adenosine receptors.

An aryl p-(trifluoromethyl) substituent increases the affinity of 1,3-disubstituted 8-phenylxanthines at A2a-adenosine receptors, while having little effect on affinity at A1-adenosine receptors. In contrast, an aryl p-(trifluoromethyl) substituent has little effect on affinity of 3,7-disubstituted and 1,3,7-trisubstituted 8-phenylxanthines. An aryl p-sulfo substituent reduces affinity of all 8-phenylxanthines at A1- and A2a-adenosine receptors. An 8-(trifluoromethyl) substituent markedly reduces affinity of 1,3-dialkylxanthines at both A1- and A2a-adenosine receptors. In contrast, 8-(trifluoromethyl)caffeine retains affinity for A2a-adenosine receptors, but does lose affinity for A1-adenosine receptors. 8-Bromo-, 8-acryl-, and 8-pent-1-enylcaffeines are also selective for A2-adenosine receptors, while 8-cyclobutylcaffeine is nonselective. 8-[trans-2-(tert-butyloxycarbonyl)vinylcaffeine is 20-fold selective for Aza vs A1 receptors.

Acylation↗
PubMed1993

Isomeric selectivity at dopamine D3 receptors.

Racemic 7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) shows greater affinity for limbic-selective dopamine D3 receptors than for more ubiquitous dopamine D2 receptors. R(+)-7-OH-DPAT was prepared and evaluated in radioreceptor assays using membranes of fibroblasts expressing the human dopamine D3 receptor as well as rat striatal membranes containing dopamine D2 receptors. This enantiomer had 2-fold greater D3 affinity than the racemate and similarly greater D3 vs. D2 selectivity (64-fold). The results may facilitate development of D3 selective agents and evaluation of functions of these receptors.

Animals↗