Receptors dopaminergic

Correlation between clinical effectiveness and receptor affinities, however, can be seen with other receptors in addition to the dopamine D2 receptor. These include other dopaminergic receptors, as well as noradrenergic and serotonergic receptors. For example, most antipsychotics also have high affinity for a -adrenoceptors and 5-HT2 receptors (225). Some antipsychotics have been shown to be selective for the adrenoceptor versus the a -adrenoceptor, for example, spiperone [749-02-0] (226) and risperidone (61) (221]... 

Catecholamines. Simphsticahy, the SNS is composed of nerves capable of synthesizing and releasing various catecholamines that can bind appropriate molecular receptors post-synapticahy. Dependent on their synthetic stmcture, they have the abhity to bind, and therefore stimulate various post-synaptic events through a, P, and dopaminergic receptors. 

Diastereomeric oxazolidines 88 and 89 (Scheme 8.4.27) were available via 1,4-reduction and cyclization of Zincke product 87, with 88 being the kinetic product under the reaction conditions and 89 (X-ray) the thermodynamically favored isomer in CDCI3 solution. Iterative reductive oxazolidine opening provided 3-aryl piperidine 91, which was readily advanced to (-)-PPP (92), a selective dopaminergic receptor antagonist. ... 

The mink Mustela vision) is a piscivorous mammal that also has been exposed to relatively high dietary levels of methyl mercury in North America in recent times. In a Canadian study, mink trapped in Yukon territory, Ontario, and Nova Scotia were analyzed for levels of mercury and abundance of muscarinic, cholinergic and dopaminergic receptors in the brain (Basu et al. 2005). A correlation was found between total Hg levels and abundance of muscarinic receptors, but a negative correlation was found between total Hg and abundance of dopaminergic receptors. Thus, it was suggested that environmentally relevant concentrations of Hg (much of it in methyl form) may alter neurochemical function. The highest levels of mercury contamination were found in mink from Nova Scotia that had a mean concentration of total Hg of 5.7 pg/g in brain, 90% of which was methyl mercury. 

Muscarinic receptor Brain binding Dopaminergic receptor binding Intracellular Ca concentration, apoptosis Cytosolic phospholipase A2 expression arachadonic acid release... 

METH-induced changes in neuropeptide levels, selective Dj (SCH 23390) and D2 (sulpiride) dopaminergic receptor antagonists were coadministered. The results are expressed as percent of control to facilitate comparisons each value represents the mean SEM of five to seven animals. Data were subjeeted to either a Student s r-test (figures 4 and 5) or ANOVA analysis followed by a multiple comparisons test (figures 1, 2, and 3). Signifieanee was set at the. 05 level. 

Administrations of five injeetions of METH (15 mg/4cg/injection 6-hour intervals between injections) caused substantial increases in the striatal and nigral levels of all three neuropeptides examined in rats sacrificed 18 hours following treatment. Figures 1 to 3 present the effects of blocking the Dj and D2 dopaminergic receptors on the responses by these peptide systems... 

Long- Evans) (W) dopaminergic receptors in striatum and nucleus 1994... 

Vauquelin G, De Keyser J, Banyingela K, Vanhaelen M. ( )Tetrahydroanisocycline and ( )tetrahydropalmatine binding to D and D2 dopaminergic receptors in human putamen. Neurochem Int 1989 15 321-324. 

Momiyama T., Sim J. A. (1996). Modulation of inhibitory transmission by dopamine in rat basal forebrain nuclei activation of presynaptic Dl-like dopaminergic receptors. J. Neurosci. 16(23), 7505-12. 

Nunes G., Jr, Tufik S., Nobrega N. (1994). Autoradiographic analysis of D1 and D2 dopaminergic receptors in rat brain after paradoxical sleep deprivation. Brain Res. Bull 34(5), 453 6. 

Alburges M., Narang N., Wamsley J. Alterations in the dopaminergic receptor system after chronic administration of cocaine. Synapse. 14 314, 1993. 

The answer is d. (Hardman, pp 407-4122) Haloperidol is a butyro phenone derivative with the same mechanism of action as the phe-nothiazines, that is, blockade of dopaminergic receptors. It is more selective for D2 receptors. Haloperidol is more potent on a weight basis than the phenothiazines, but produces a higher incidence of extrapyra-midal reactions than does chlorpromazine. 

Sibley, D. R. New insights into dopaminergic receptor function using antisense and genetically altered animals. Annu. Rev. Pharmacol. Toxicol. 39 313-341,1999. 

Dopamine produces dose-dependent hemodynamic effects because of its relative affinity for cq-, /Jr, /J2-, and Dr (vascular dopaminergic) receptors. Positive inotropic effects mediated primarily by / -receptors become more prominent with doses of 2 to 5 mcg/kg/min. At doses between 5 to 10 mcg/kg/min, chronotropic and -mediated vasoconstricting effects become more prominent. Especially at higher doses, dopamine alters several parameters that increase myocardial oxygen demand and potentially decrease myocardial blood flow, worsening ischemia in some patients with coronary artery disease. 

Indolopiperidines were described as CCR2 antagonists, and compound 25 was reported to be potent (CCR2 Bnd Kj = 50 nM) and selective versus CCR5. However, it also displayed unwanted activity at the 5-HT and dopaminergic receptors [100]. Important functionality included the phenol (giving a 10-fold... 

Giacomelli S, Palmery M, Romanelli L, Cheng CY, Silvestrini B. (1998). Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro. Life Sci. 63(3) 215-22. 

Fig. 9.8 Examples of rule-of-three compliant molecules that have biological activity better than 10 nM. Under each molecule, the following information is included molecule name, MW, ClogP, the biological activity type, value and target. Target names are as follows D3 and D4 - dopaminergic receptor types 2 and 3 AChE and BChE - acetyl- and butyryl-choline esterases PRa and PRb - progesterone receptor types A and B H] and H3, histamine receptor types 1 and 3 5-HT2a, 5-HT2b, 5-HT2c, 5-HT3, 5-HT4 - serotonin receptor subtypes 2A, 2B, 2C, and types 3 and 4 DAT, NET, 5-HTT - dopamine, norepinephrine and serotonin transporter proteins /X], /x.2, S, ki, ks - opioid receptor types mu-1, mu-2, delta, kappa-1 and kappa-3 5a-Rl and 5o -R2 - 5-alpha-reductase isozymes 1 and 2 Flt-1-fms-like tyrosine kinase receptor.

A number of different compounds of the piperidine and piperazine series with p-fluorobuty-rophenone group substitutions at the nitrogen atom display significant neuroleptic activity (haloperidol, trifluperidol, droperidol, methorin). There is a considerable interest in butyrophenone derivatives as antipsychotic agents as well as in anesthesiology. They exhibit pharmacological effects and a mechanism of action very similar to that of phenothiazines and thioxanthenes in that they block dopaminergic receptors. However, they are more selective with respect to D2 receptors. 

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