Dopamine receptors, classes

Ach, acetylcholine CNS, central nervous system CD, carbidopa COMT, catechol-O-methyltransferase D1, a class of dopamine receptors which includes D, and D5 subtypes D2, a class of dopamine receptors which includes D2, D3, and D4 subtypes DA, dopamine LD, levodopa MAO, monoamine oxidase MD, maintenance dose NMDA, N-methyl-D-aspartate. 

Membrane-associated receptors are linked to transducing proteins (like G-proteins) in the inner portion of the membrane. G-protein coupled receptor (GPCR) families comprise a major class of the receptors that are pharmacologically relevant, such as muscarinic acetyl choline receptors, adrenoceptors, dopamine receptors, serotonine, opiate, peptide hormone, purinerg receptors, and also sensory chemoreceptors. A large variety of subtypes are described in the pharmacological literature. 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

All of the known class A receptors are subject to posttranslational modification at one or more iV-linked glycosylation sequences, found either in the extracellular amino terminns or in the second exdacellular loop. Glycosylation is required for the expression of some GPCRs at the plasma membrane (12,13). Furthermore, many receptors, snch as rhodopsin and the dopamine receptors, are also subject to other posttranslational modifications, such as palmitoylation at the intracellular domains... 

Some first-generation agents, such as haloperidol, are rather specific for one subtype of dopamine receptor, D2. This suggests that some degree of both efficacy and side effects are associated with dopamine antagonism at this receptor. However, the situation is complex, as usual. There are five classes of dopamine receptors known Di through D5. To complicate matters further, several of these classes have subclasses. In total, there are at least 15 dopamine receptors. Which of these is important for relief of the symptoms of schizophrenia Which is responsible for movement disorders The answers to these questions are incomplete. We do have a few hints. 

It also seems plausible that antipsychotic drugs competitively bind with dopamine receptors and block the action of dopamine on corresponding receptor sites, thus lowering psychotic activity. Central dopamine receptors are subdivided into Dj, D2, and according to some sources, Dj receptors. These receptors have a high affinity for dopamine, but they differ in sensitivity to neuroleptics of various chemical classes. For example, drugs of the phenothiazine series are nonselective competitive Dj and D2 antagonists. Unlike phenoth-iazines, antipsychotics of the butyrophenone series such as haloperidol display selective action only on D2 receptors. 

Several classes of drugs, notably the antipsychotics, discussed in Chapter 34, interfere with dopaminergic transmission. In general, dopamine appears to be an inhibitory neurotransmitter. Five dopamine receptors have been identified the most important and best studied are the Dj. and D2.receptor groups. The Dj receptor, which increases cyclic adenosine monophosphate (cAMP) by activation of adenylyl cyclase, is located primarily in the region of the putamen, nucleus accum-bens, and in the olfactory tubercle. The D2 receptor decreases cAMP, blocks certain calcium channels, and opens certain potassium channels. 

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. 

Of the drugs used for treating parkinsonism, the anticholinergics are the only class that can provide benefit in the treatment of the drug-induced parkinsonism seen with antipsychotic therapy. This is because the blockade of dopamine receptors by the antipsychotics leads to increased activity of the striatal neurons. Blockade of the muscarinic receptors reduces this excitatory activity. 

Many compounds have been evaluated for their effects on brain metabolism (London, 1993). A surprisingly limited number of common regional metabolic effects have been seen within drug classes. Antipsychot ics, especially the older typical antipsychotics, tend to be associated with changes in striatal metabolism consistent with the high density of D2 dopamine receptors in those brain structures (Cohen et al.. 1999). On the other hand, quite different patterns of metabolic effects have been seen following acute doses with paroxetine and fluoxetine, both of which are selective serotonin... 

It belongs to azapirones which is chemically and pharmacologically distinct class. It acts as a partial agonist at serotonin and dopamine receptors and having no hypnotic and sedative action. It does not interact with benzodiazepine receptor or modify GABA-ergic transmission. 

The ratio between the blockade of serotonin receptors and dopamine receptors differs for various classes of antipsychotic drugs. True or False. 

Receptor Class Mu (pi) Primary Therapeutic Effect(s) Spinal and supraspinal analgesia Other Effects Sedation respiratory depression constipation inhibits neurotransmitter release (acetylcholine, dopamine) increases hormonal release (prolactin growth hormone)... 

---