Dopamine features

As with other monoamines, the actions of 5-HT are terminated by its reuptake from the synapse by another member of the family of Na+/CU-dependent transporters. The 5-HT transporter has many features in common with its catecholamine equivalent (described fully in Chapter 8 see Fig. 8.7), including its presumed 12 transmembrane-spanning domains. However, the cloned 5-HT transporter has a for 5-HT of about 450 nM whereas its K for both noradrenaline and dopamine is some ten thousand-fold greater (Povlock and Amara 1997) which means that it is relatively selective for uptake... 

The chemical structure of histamine has similarities to the structures of other biogenic amines, but important differences also exist. Chemically, histamine is 2-(4-imidazolyl)ethylamine (Fig. 14-1). The ethylamine backbone is a common feature of many of the amine transmitters (e.g. dopamine, norepinephrine and serotonin). However, the imidazole nucleus, absent from other known transmitters, endows histamine with several distinct chemical properties. Among these is prototypic tautomerism, a property that permits it to exist in two different chemical forms (Fig. 14-1). The tautomeric properties of histamine are thought to be critical in the... 

Dystonia due to identifiable structural or biochemical abnormalities ( secondary dystonia) often occurs weeks or months after strokes or other focal lesions, which commonly involve the basal ganglia, but may also involve the thalamus or cerebellum. Dystonia is also seen in children with cerebral palsy and in patients with abnormalities of dopaminergic transmission. For instance, dystonia may develop in the context of Parkinson s disease, either as an early parkinsonian sign, or in response to dopaminergic drugs. A particularly interesting inherited disease results in a combination of dystonia and parkinsonian features at a young age, which responds dramatically to treatment with low-dose levodopa ( dopamine-responsive dystonia ). 

The two hallmark features in the substantia nigra pars compacta are loss of neurons and the presence of Lewy bodies. There is a positive correlation between the degree of nigrostriatal dopamine loss and severity of motor symptoms. PD is relatively asymptomatic until profound depletion (70% to 80%) of substantia nigra pars compacta neurons has occurred. 

Holland PC (1991) Acquisition and transfer of occasion setting in operant feature positive and feature negative discriminations. Learn Motiv 22 366-387 Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine-release in the limbic system of freely moving rats. Eur J Pharmacol 132 337-338 James JR, Villanueva HE, Johnson JH, Arezo S, Rosecrans JA (1994) Evidence that nicotine can acutely desensitize central nicotine acetylcholinergic receptors. Psychopharmacology 114 456-462... 

Reward Therapy. A similar (yet nonspecific) approach is to use a medication that stimulates the brain s reward centers. Reward medications usually do not work in quite the same way as the substance of abuse however, the net effect in the final common pathway (i.e., the reward centers) may be the same. For the most part, these reward centers are activated by either dopamine or endogenous opioid agonists. One common feature of most abused drugs is that they stimulate these reward centers. This lies at the heart of their addictive potential. Some attempts have been made to use medications that activate these reward centers in place of the abused substance. The hypothesis is that the addict will have less intense craving for his/her preferred substance of abuse in the presence of these other agents. This is, of course, a relatively nonspecific approach that could theoretically be used to treat the abuse of many different substances. It has not yet, however, demonstrated any utility in the treatment of substance abuse. 

Humber, L.G., Bruderlin, F.T., Philipp, A.H., Gotz, M., Voith, K. Mapping the dopamine receptor. 1. Features derived from modifications in ring E of the neuroleptic butadamol./. Med. Chem. 1979, 22, 761-767. 

As drugs of mixed action, amphetamines activate adrenergic receptors and simultaneously release endogenic catecholamines (norepinephrine and dopamine) from neurons of the brain and periphery. Sympathomimetic effects on the periphery are very similar to those of ephedrine. Amphetamine elevates systolic and diastolic blood pressure and has weakly expressed, broncholytic action. These effects are more prolonged, yet less expressed, than with epinephrine. The distinctive feature of amphetamines is their psychostimulatory activity. Larger doses can cause hallucinations and mental conditions similar to paranoid schizophrenia. As a sympathomimetic, amphetamine is sometimes used for uterine inertia. Synonyms of amphetamine are phenamine and benzedrine. 

Solms (2000 see also Chapter 7) has observed that suppression of cortical dopaminergic afferents abolishes dreaming. Dopamine therefore appears to be a neurotransmitter keystone of the common features of REM sleep, dreaming and schizophrenia. 

These systems are also described as normal copper proteins due to their conventional ESR features. In the oxidized state, their color is light blue (almost undetectable) due to weak d-d transitions of the single Cu ion. The coordination sphere around Cu, which has either square planar or distorted tetrahedral geometry, contains four ligands with N and/or 0 donor atoms [ 12, 22]. Representative examples of proteins with this active site structure (see Fig. 1) and their respective catalytic function include galactose oxidase (1) (oxidation of primary alcohols) [23,24], phenylalanine hydroxylase (hydroxy-lation of aromatic substrates) [25,26], dopamine- 6-hydroxylase (C-Hbond activation of benzylic substrates) [27] and CuZn superoxide dismutase (disproportionation of 02 superoxide anion) [28,29]. 

The agents in this class demonstrate the common feature of specific inhibition of serotonin reuptake without significant effects on norepinephrine and dopamine reuptake. These agents also lack direct agonist or antagonist activity on any neurotransmitter receptor. 

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