Prejunctional Dopamine Receptor Stimulants
M.D. Francesco Amenta in Peripheral Dopamine Pathophysiology, 2019
The question as to whether or not bromocriptine stimulates DA1 receptors remains controversial. Positive evidence has been obtained in isolated, precontracted vessels, i.e., dose-dependent relaxation of mesenteric and middle cerebral arteries of the rabbit, and dilation of vessels in the perfused, denervated rat kidney occur within the same concentration range as that required to produce comparable effects with dopamine. The vasorelaxant effects of both agonists are attenuated by a variety of DA receptor antagonists ([ + ] butaclamol, droperidol, metoclopramide, haloperidol, ergometrine, apomorphine), whereas (-) butaclamol and β-adrenoceptor antagonists are ineffective.62-66 Such findings are, however, difficult to reconcile with the compound’s lack of stimulant activity on DA-sensitive adenylate cyclase in homogenates of bovine retina and rat striatum. In both tissues, it acts only as a competitive antagonist of the effects of DA.16,67
Imaging Neuroreceptors to Study Drug Action in Living Human Brain
Edythe D. London in Imaging Drug Action in the Brain, 2017
These criteria largely carry over from in vitro homogenate binding studies. They include the following: Saturability of the receptor site by the radioligand of interest. Increasing doses of the unlabeled ligand reduce the binding of the labeled radioligand in a dose-dependent fashion.Appropriate competition by various radioligands known to bind to the receptor of interest. This criterion includes stereospecificity. For example, (+) -butaclamol blocks the binding of 11C-N-methylspiperone (11C-NMSP), whereas (–) -butaclamol has a much lower affinity for the D2 dopamine receptor and does not substantially compete with 11C-NMSP.Regional distribution of the radioligand consistent with the known pattern of neuroreceptors. This criterion is dependent on the pharmacokinetics of the radioligand and assumes that the compound has reached equilibrium with the receptor sites.
Dopamine Receptor Studies with Positron Emission Tomography
W. R. Wayne Martin in Functional Imaging in Movement Disorders, 2019
Several points regarding the nonsteady-state method need emphasis. First, it is assumed that nonspecific binding in the cerebellum is the same as in the striatum. Implicit in this assumption is that no specific binding occurs in cerebellum. Logan et al.36 show that stereoselective blocking with (+) butaclamol (which blocks D2 dopaminergic receptors) reduces the uptake of 18F-spiperone in cerebellum and suggest that this indicates the presence of saturable binding sites. It is important to note that the difference was demonstrable only at relatively late times after injection. The impact of the resulting error in the estimate of nonspecific binding (actually the estimate of the free fraction in compartment 2, f2), results in a modest error in the estimate of the combined forward rate constant (the product of ka and Bmax).47 From a practical point of view, the greatest disadvantage of using the nonsteadystate method with 18F-spiperone is the length of time required for the study, at least 2 to 3 h after radioligand injection.36,37,47 Hopefully, a ligand with faster kinetics (i.e., rapid association and reversibility), such as raclopride, would permit a much shorter study.42
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.