Dopamine system

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

G-protein-coupled Receptors Dopamine System Adenosine Receptors Chemokine Receptors... 

Adrenerigic System Dopamine System Histaminergic System Antidepressant Dtugs... 

The dopamine system constitutes the cellular and biochemical network that is involved in the synthesis, release, and response to dopamine. In general, this involves cells that express significant levels of tyrosine hydroxylase (TH) and limited amounts of dopamine (3-hydioxylase [1]. Dopamine-responsive cells express receptors specifically activated by this neurotransmitter, which are known as dopamine Dl, D2, D3, D4, and D5 receptors [2, 3]. 

Acnte Drag Action/Drng Reinforcement and the Mesolimbic Dopamine System... 

Dopamine System Histaminergic system Muscarinic Receptors Serotoninergic System Tachykinins and their Receptors... 

Antipsychotic Drugs Dopamine System Synaptic Transmission... 

The main target of action of methylphenidate, the most widespread clinically used psychostimulant, is the dopamine transporter (DAT) its inhibition increases intrasynaptic dopamine concentrations. The subcortical dopamine system (mesolimbic and nigrostriatal parts) mediates the unconditioned and conditioned responses toward reinforcement. 

Psychostimulants. Table 1 Properties of cortical versus striatal dopamine system... 

Nicotine is the main psychoactive ingredient of tobacco and is responsible for the stimulant effects and abuse/ addiction that may result form tobacco use. Cigarette smoking rapidly (in about 3 sec ) delivers pulses of nicotine into the bloodstream. Its initial effects are caused by its activation of nicotinic acetylcholine (nACh) receptors. nACh receptors are ligand-gated ion-channels and pre- and postsynaptically located. Reinforcement depends on an intact mesolimbic dopamine system (VTA). nACh receptors on VTA dopamine neurons are normally activated by cholinergic innervation from the laterodorsal tegmental nucleus or the pedunculopontine nucleus. 

Another theory for the action of stimulant diugs in ADHD involves effects on nonstiiatal monoamine systems. Frontal cortical dopamine, norepinephrine, and serotonin are clearly important in cognitive functioning and impulse control. These neurotransmitters directly modulate reward-related behaviors associated with the striatal dopamine system. Moreover, the amygdala may be pharmacologically influenced leading to enhanced... 

Dysfunction of cortical-subcortical dopamine systems is associated with an impaired inhibitory control after chronic drug administration. 

Taylor JR, Jentsch JD (2001) Stimulant effects on striatal and cortical dopamine systems involved in reward-related behavior and impulsivity. In Solanto MV, Arnsten AFT, Castellanos FX (eds) Stimulant drugs and ADHD, Oxford University Press, pp 104-133... 

L-DOPA/Levodopa Dopa Decarboxylase Dopamine System Dopamine- 3-hydroxylase Dopaminergic Neurotoxicity Dose... 

Nath A, Jones M, Maragos W, Booze R, Mactutus C, BeU J, Hauser KF, Mattson M (2000) Neurotoxicity and dysfunction of dopamine systems associated with AIDS dementia. Psychopharmacol 14 222-227... 

While the nigrostriatal pathways are ipsilateral some crossing occurs in fibres from the ventral tegmental AlO nucleus. These pathways are shown diagramatically in Fig. 7.1. Further details can be obtained from Moore and Bloom (1978) and Lindvall and Bjorkland (1978). The nuclei provide distinct loci for activating the dopamine systems for electrophysiological, release and behavioural studies and for their destruction by electrolytic lesion or injection of the toxin 6-hydroxydopamine (6-OHDA). 

Moore, RY and Bloom, FE (1978) Central catecholamine neuron systems, anatomy and physiology of the dopamine system. Ann. Rev. Neurosci. 1 129-169. 

Ungerstadt, U and Arbuthnott, GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxy dopamine lesions of the nigrostriatal dopamine system. Brain Res. 24 485-493. 

D Mello, G.D. Comparison of some behavioral effects of and electrical brain stimulation of the mesolimbic dopamine system in rats. Psychopharmacology (Berlin) 75 184-192, 1981. 

Iversen, S. Brain dopamine systems and behavior. In Iversen. L. ... 

Both amphetamine and cocaine have also been reported to support intracranial self-administration in the mesolimbic/mesocortical dopaminergic system. Rats will self-administer cocaine into the medial prefrontal cortex (Goeders and Smith 1983). while amphetamine is self-administered into the orbitofrontal cortex of rhesus monkeys (Phillips and Rolls 1981) and the nucleus accumbens of rats (Hoebel et al. 1983 Monaco et al. 1981). These data indicate that the mesolimbic/mesocortical dopaminergic system is involved in the initiation of stimulant reinforcement processes, and this work suggests that the region of the nucleus accumbens, more specifically the mesolimbic dopamine system, may be an important substrate for reinforcing properties of several psychomotor stimulant drugs. 

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