China
Africa
Explore chapters and articles related to this topic
Dopamine Receptor Studies with Positron Emission Tomography
Published in W. R. Wayne Martin, Functional Imaging in Movement Disorders, 2019
Another important consideration common to in vitro and in vivo assays is radioligand specificity. Spiperone and its labeled derivatives specifically bind predominantly to D2 dopaminergic sites and S2 serotonergic sites.39–41 Fortunately, these different receptor sites are, to a degree, anatomically separate. D2 sites predominate in striatum, and S2 sites predominate in frontal cortex.39–43 The degree of anatomic separation may have important species variability. Furthermore, relative distribution of receptor types potentially could change under pathologic conditions. Thus, one must cautiously interpret alterations in receptor binding based upon normal distributions. Alternatively, radioligands with greater specificity would limit this potential source of error. For example, 11C-raclopride has greater specificity for D2 dopaminergic sites with much lower affinity for serotonergic receptors.42 Recently, 11C-labeled SCH 23390 has been synthesized for use in PET studies.33 This radioligand has relatively high specificity for D, dopaminergic receptor sites and will permit its evaluation with the development of proper methodology.
Localizing Drug and Neurotransmitter Receptors in Vivo with Tritium-Labeled Tracers
Published in William C. Eckelman, Lelio G. Colombetti, Receptor-Binding Radiotracers, 2019
Identification of receptors by binding techniques has proven tremendously beneficial for furthering our knowledge of receptors. In these many studies it has become apparent that one must exercise extreme caution in accepting a binding site as a receptor. First, there is the issue of receptor vs. nonreceptor binding. There have been several instances when a binding site having some properties normally associated with a receptor has been found to be unrelated to receptor. For example, in many studies it has been shown that various receptors show chemical stereospecificity. In early receptor-binding studies, stereospecificity was regarded as the hallmark criterion of receptor binding. However, in later studies it was shown that stereospecificity was not totally adequate as a hallmark feature for identifying receptor binding. Stereospecific binding of radioactive drugs has been described for even inert materials such as glass fiber filters.11 In addition, it has been shown that drugs bind to a multiplicity of receptors. While this issue is somewhat different from the receptors versus nonreceptor issue, it does relate to the critical issue of selectivity. For example, investigators originally thought spiperone was highly selective for dopamine receptors in brain.12,13 It has since been shown however that spiperone binds to both serotonin and noradrenergic alpha receptors as well.14,15 Thus, it is important to realize that one has to rule out various pitfalls and problems and that binding can occur both to nonreceptor sites as well as to multiple receptor sites.
Imaging Neuroreceptors to Study Drug Action in Living Human Brain
Published in Edythe D. London, Imaging Drug Action in the Brain, 2017
The process by which potential radiopharmaceuticals are identified and are subsequently studied for biological appropriateness in animals and finally in humans, is a complicated and technical matter. It begins with unlabeled compounds (e.g., drugs as spiperone, a neuroleptic employed in treating schizophrenic patients). The radioactive tracers of carbon, nitrogen, and oxygen replace these common atoms in biological molecules; 18F is sometimes an appropriate substitute for hydrogen atoms.
Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission
Published in Inhalation Toxicology, 2023
María-de-los-Angeles Andrade-Oliva, Yazmín Debray-García, Guadalupe-Elide Morales-Figueroa, Juan Escamilla-Sánchez, Omar Amador-Muñoz, Raúl V. Díaz-Godoy, Michael Kleinman, Benjamín Florán, José-Antonio Arias-Montaño, Andrea De Vizcaya-Ruiz
For the competition assay, membranes (one preparation per animal) were incubated for 90 min at 25 °C in incubation buffer containing 2 nM [3H]-spiperone and increasing concentrations of dopamine (eight concentrations, 10−9 to 10−4 M, triplicate determinations). Non-specific binding was determined in the presence of 100 nM (±)-butaclamol. The incubation buffer was supplemented with 100 nM ketanserin (to prevent [3H]-spiperone from binding to 5-HT2 receptors) and 10 μM pargyline/200 μM ascorbic acid to prevent dopamine degradation. Incubations were terminated by rapid filtration through GF/B filters presoaked in 0.3% polyethylenimine for 2 h. Filters were soaked in 3 ml of scintillation liquid, and the tritium content was determined by scintillation counting. The protein content was determined by a bicinchoninic acid assay (BCA; Pierce, Rockford, IL, USA) with BSA as a standard.
Dopamine-induced functional activation of Gαq mediated by dopamine D1-like receptor in rat cerebral cortical membranes
Published in Journal of Receptors and Signal Transduction, 2019
Yuji Odagaki, Masakazu Kinoshita, Toshio Ota
The inhibitory effects of several compounds were also determined for the increases in specific [35S]GTPγS binding to Gαq in rat cerebral cortical membranes induced by 100 nM SKF83566, 1 μM R(+)-SCH23390, and 10 μM pergolide (Figure 7(a)). In all three cases, the response was inhibited potently by the compounds with high affinity for 5-HT2A receptors (risperidone, MDL100907, and spiperone), whereas the inhibitory effects of the selective dopamine D1-like receptor antagonist SCH39166 [24] were comparatively weak (Table 2). When the pKb values of these compounds for pergolide-stimulated binding were compared with those determined for dopamine- or 5-HT-stimulated [35S]GTPγS bindings to Gαq, there was a highly significant correlation with those for 5-HT-stimulated binding, but not with those for dopamine-stimulated binding (Figure 7(b)). Likewise, there was a highly significant correlation between the pKb values for SKF83566-stimulated binding and those for 5-HT-stimulated binding. In the case of R(+)-SCH23390-stimulated [35S]GTPγS bindings to Gαq, Pearson’s correlation coefficient yielded a tendency of significant correlation with the pKb values for 5-HT-stimulated binding (r = 0.53, p = .076). The results of correlation analysis are summarized in Table 3.
The sigma-2 (σ-2) receptor: a review of recent patent applications: 2013–2018
Published in Expert Opinion on Therapeutic Patents, 2018
Benjamin E. Blass, John Patrick Rogers
Studies on the binding patterns of a variety of drugs in membrane preparations using [3H](±)-ethylketocyclazocine (5), [3H]SKF-10,047, [3H]haloperidol (6), [3H]PCP and [3H]spiperone (7) (Figure2) conducted by Tam et al. [4] further refined the characteristics of the sigma receptor, but the lack of a sigma receptor selective ligand was a limiting factor. The identification of di-o-tolylguanidine (DTG, 8) (Figure 3) as a highly potent, selective sigma receptor binder and subsequent studies using [3H]-DTG by Weber et al. provided clear radiolabeling data that clearly distinguished the sigma receptor from other receptors [5]. A second potent, selective sigma binder, (+)-pentazocine (9) (Figure 3), facilitated the discovery of the two subtypes of the sigma receptor by Bowen et al. This compound potently binds to the sigma-1 receptor (Ki = 7 nM), but is far less potent at the sigma-2 receptor (Ki = 1361 nM). This is in stark contrast to DTG, which is nearly equipotent at both the sigma-1 (Ki = 74 nM) and the sigma-2 (Ki = 61 nM) receptors [6].