Action dopamine

Higashi, H., Inanaga, K., Nishi, S., Uchimura, N. Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre-treatment. J. Physiol. 408 587, 1989. 

Dopamine is a catecholamine (see Chapter 10 and Fig. 31.2) whose actions are mediated by dopamine receptors that are classified as Dj-like (Dj, D5) or D2-like (D2, D3, D4). Dopamine actions on Dj receptors exert an excitatory effect, whereas the actions of dopamine on D2 receptors inhibit neuronal activity. The loss of striatal dopamine produces an imbalance in information processing in the neostriatum that modifies transmission in other basal ganglia regions. Also important in neural transmission are the striatal interneurons that are found within the confines of the striatum, that use the excitatory neurotransmitter acetylcholine, and that modulate the activity of striatal output neurons. 

The inabihty of the neurons to eliminate the oxidative load may result in a self-perpetuating cycle of oxidative damage that ultimately leads to neuronal death. One source of oxidative stress may be dopamine metabolism (Fig. 31.2). The excessive excitatory activity in the substantia nigra created by the loss of dopamine actions within the striatum could lead to excitotoxicity that is mediated by glutamate. 

Bromocriptine Inhibits adenylyl cyclase and interacts with other intracellular pathways Restores dopamine actions in the central nervous system Parkinson s disease, prolactinemia Oral Toxicity Nausea, headache, orthostatic hypotension... 

Aperia A. Dopamine action and metabolism in the kidney. Current Opinion in Nephrology and Hypertension 1994 3 39-45. 

Serotonin and dopamine reuptake inhibition. Dual reuptake blockers of both serotonin and dopamine are in clinical testing. Although the SSRI sertraline has some dopamine reuptake inhibition as well as more potent serotonin reuptake inhibition, minaprine and bazinaprine have more potent dopamine actions and are thus dual sero-tonin/dopamine agents. 

Dopamine actions and pharmacological implications (A). In the CNS, dopamine serves as a neuromediator. Dopamine receptors are also present in the periphery. Neuro-nally released dopamine can interact with various receptor subtypes, all of which are coupled to G-proteins. Two groupings can be distinguished the family of Dq-like receptors (comprising subtypes Dq and D5) and the family of D2-lilsignal transduction pathways. Thus, synthesis of cAMP is stimulated by D-i-like receptors but inhibited by D2-lil[Pg.116]

Increases norepinephrine and especiaiiy dopamine actions by biocking their reuptake and faciiitating their reiease... 

Enhancement of dopamine actions in other brain regions (e.g., basal ganglia) may improve hyperactivity... 

Increases norepinephrine and especially dopamine actions by blocking their reuptake and facilitating their release... 

CNS side effects presumably due to excessive dopamine actions... 

The discovery that the first antipsychotic drugs in the early 1950s, such as chlorpromazine, work in vitro by blocking dopamine receptors led to the hypothesis that schizophrenia was the result of excessive dopaminergic neurotransmission (54, 55). Supporting this hypothesis, dmgs that enhance dopamine action (e.g., cocaine, amphetamines, and L-DOPA) worsen the symptoms of schizophrenia. However, it is clear that 1) not all patients respond to neuroleptic treatment and 2) not all symptoms are reversed by the medication. 

Sonsalla, P.K. Gibb, J.W. and Hanson, G.R. Nigrostriatal dopamine actions on the D2 receptors mediate methamphetamine effects on the striatonigral Substance P system. Neuropharmacology 25 1221-1230, 1986. 

Strickland et al. (1991, 1994) studied the effects of ergot and loline alkaloids of E+ fescue on prolactin release by isolated and perfused rat pituitary cells. The ergot alkaloids had prolactin-lowering effects and mimicked dopamine action. The use of a D2 dopamine receptor antagonist (domperidone) blocked the effect of the ergot alkaloids and prevented their prolactin-lowering effect. Domperidone... 

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