Dopamine receptor postsynaptic

Psychostimulants. Figure 2 Dopamine molecules have two different possible targets. Both ways are initially increased by DAT inhibition caused by methylphenidate pre- and postsynaptic dopamine receptors. Stimulation of postsynaptic receptors results in inhibition of presynaptic action potential generation. On the other hand, presynaptic receptor stimulation leads to a transmission inhibition of action potentials. Therefore, both mechanisms are responsible for a decrease in vesicular depletion of dopamine into the synaptic cleft (adapted from [2]). 

The exact mechanism of action of these dm is not understood. It is thought that these drug s act directly on postsynaptic dopamine receptors of nerve cells in the brain, mimicking die effects of dopamine in the brain. 

Markstein, R., and Lahaye, D. In vitro effect of the racemic mixture and the (-)enantiomer of N-n-propyl-3(3-hydroxyphenyl)-piperidine (3-PPP) on postsynaptic dopamine receptors and on a presynaptic dopamine autoreceptor. J. Neural Transm 58 43-53, 1983. 

Mulder, A.H. Draper, R. Sminia, P. Schoffelmeer, A.N.M. and Stoof, J.C. Agonist and antagonist effects of 3-PPP enantiomers on functional dopamine autoreceptors and postsynaptic dopamine receptors in vitro. jji J. Pharmacol 107 291 -297, 1985. 

Volkow N., Fowler J., Wolf A. et al. Effects of chronic cocaine abuse on postsynaptic dopamine receptors. Am. J. Psychiatry. 147 719, 1990. 

Drugs stimulate receptors on the cell bodies of dopaminergic neurons causing dopamine release and stimulating postsynaptic dopamine receptors in the nucleus accumbens, supposedly resulting in the perception of pleasure [1]. Other hypotheses suggest that these mesolimbic dopaminergic pathways are necessary for the... 

Tardive dyskinesia is a condition that sometimes results from chronic neuroleptic treatment lasting from months to years (Baldessarini 1996 Stahl et al. 1982). It occurs in 15-25% of treated chronic psychotic patients and is characterized by repetitive, athetoid writhing and stereotyped choreiform movements of the face, eyes, mouth, extremities, and trunk. Discontinuation of neuroleptic medication allows the symptoms to gradually decline, but sometimes they can persist indefinitely. The pathophysiology of tardive dyskinesia is poorly understood, but it appears to involve supersensitive postsynaptic dopamine receptors in the basal ganglia. 

Pharmacology Pergolide mesylate is a potent dopamine receptor agonist at both D- and D2 receptor sites. In Parkinson disease, pergolide is believed to exert its therapeutic effect by directly stimulating postsynaptic dopamine receptors in the nigrostriatal system. 

Another form of parkinsonism is drug-induced, that is, iatrogenic parkinsonism, which often is a comphca-tion of antipsychotic therapy, especially following the use of the butyrophenone and phenothiazine drug classes (see Chapter 34). Unlike idiopathic parkinsonism, striatal content of dopamine is not reduced by administration of these drugs. In contrast, they produce a functional decrease in dopamine activity by blocking the action of dopamine on postsynaptic dopamine receptors. 

Mechanism of Action A phenothiazine that blocks dopamine neurotransmission at postsynaptic dopamine receptor sites. Possesses strong anticholinergic, sedative, and antiemetic effects moderate extrapyramidal effects and slight antihistamine action. Therapeutic Effect Relieves nausea and vomiting improves psychotic conditions controls intractable hiccups and porphyria. 

Mechanism of Action A general anesthetic and antiemetic agent that antagonizes dopamine neurotransmission at synapses by blocking postsynaptic dopamine receptor sites partially blocks adrenergic receptor binding sites. Therapeutic Effect Produces tranquilization, antiemetic effect. 

Mechanism of Action An antipsychotic, antiemetic, and antidyskinetic agent that competitiveiy biocks postsynaptic dopamine receptors, interrupts nerve impulse movement, and increases turnover of dopamine in the brain. Has strong extrapyrami-dai and antiemetic effects weak antichoiinergic and sedative effects. Therapeutic Effect Produces tranquiiizing effect. 

Mechanism of Action An antipsychoticagent and antiemetic that blocks postsynaptic dopamine receptor sites in the brain. Therapeutic Effect Suppresses behavioral response in psychosis, and relieves nausea and vomiting. 

Despite a number of necessary refinements in later years, the dopamine hypothesis in its simple original version ( neuroleptics act via blockade of postsynaptic dopamine receptors ) is still consistent with many pharmacological and clinical observations, such as ... 

Reserpine depletes cerebral dopamine by preventing intraneuronal storage (see Chapter 6) it is introduced in low doses (eg, 0.25 mg daily), and the daily dose is then built up gradually (eg, by 0.25 mg every week) until benefit occurs or adverse effects become troublesome. A daily dose of 2-5 mg is often effective in suppressing abnormal movements, but adverse effects may include hypotension, depression, sedation, diarrhea, and nasal congestion. Tetrabenazine (12.5-50 mg orally three times daily) resembles reserpine in depleting cerebral dopamine and has less troublesome adverse effects it is now available in the USA. Treatment with postsynaptic dopamine receptor blockers such as phenothiazines and... 

FIGURE 23.7 Dopamine (DA) is synthesized within neuronal terminals from the precursor tyrosine by the sequential actions of the enzymes tyrosine hydroxylase, producing the intermediary L-dihydroxyphenylalanine (Dopa), and aromatic L-amino acid decarboxylase. In the terminal, dopamine is transported into storage vesicles by a transporter protein (T) associated with the vesicular membrane. Release, triggered by depolarization and entry of Ca2+, allows dopamine to act on postsynaptic dopamine receptors (DAR). Several distinct types of dopamine receptors are present in the brain, and the differential actions of dopamine on postsynaptic targets bearing different types of dopamine receptors have important implications for the function of neural circuits. The actions of dopamine are terminated by the sequential actions of the enzymes catechol-O-methyl-transferase (COMT) and monoamine oxidase (MAO), or by reuptake of dopamine into the terminal. 

Helmreich I, Reimann W, Hertting G, Starke K (1982) Are presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in the rabbit caudate nucleus pharmacologically different Neuroscience 7 1559-66... 

Abnormal involuntary movements appear in approximately 50% of patients within the first few months of the commencement of L-dopa therapy, these effects being correlated with the dose of the drug and the degree of clinical improvement. The frequency of the abnormal involuntary movements increases with the duration of administration and can reach 80% of patients after 1 year of therapy. Such abnormal movements are presumed to be due to postsynaptic dopamine receptor hyperactivity and include buccolingual movements, grimacing, head-bobbing, and various choreiform and dystonic movements of the extremities. Tolerance does not appear to develop to these effects and there is no known treatment apart from reducing the dose of L-dopa, a situation which inevitably leads to the likelihood of a return of the Parkinsonian symptoms. 

Kim, H. S., Jang, C. G., and Park, W. K. (1996). Inhibition by MK-801 of morphineinduced conditioned place preference and postsynaptic dopamine receptor supersensitivity in mice. Pharmacol. Biochem. Behav. 55, 11-17. 

In any case, such direct binding measures of the dopamine receptor in the AP provides new dimensions in the understanding of the functional role of dopamine in the gland. The detailed examination of the dynamics of the dopamine receptor in the AP offers the simplest model of studying postsynaptic dopamine receptors in isolation and will further our understanding of dopamine receptor-transduced signals in the brain. 

Dopamine induces biochemical and physiological effects in the mammalian neostriatum. The occurrence of a D-l dopamine receptor (in the classification scheme of Kebabian and Caine) accounts for the ability of dopamine to enhance cyclic AMP formation. The occurrence of a D-2 dopamine receptor accounts for the ability of dopamine to inhibit cyclic AMP formation brought about by stimulation of a D-l dopamine receptor. Dopamine receptors mediate the regulation of (1) the release or turnover of acetylcholine (postsynaptic dopamine receptor) and (2) the release or turnover of dopar mine (presynaptic autoreceptor). Both receptors can be classified as D-2 dopamine receptors. Indications for the occurrence of dopamine receptors affecting the release or turnover of GABA, glutamate, serotonin and several neuropeptides are evaluated. 

A Postsynaptic Dopamine Receptor Regulating the Release car Turnover of Acetylcholine... 

Many of these effects can still be observed after pretreatment with kainic acid in the neostriatum (113). This treatment degenerates the neostriatal efferent pathways and by consequence also the neostriatal efferent part(s) of the nigrostriatal loop. Apparently postsynaptic dopamine receptors, if located on these striatonigral neurons play only a minor role in the regulation of dopamine synthesis and turnover in dopaminergic neurons and the major role has to be attributed to dopaminergic autoreceptors. 

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