Dopamine, dose-response curve

Other drug effects that decrease DA activity also support this position. Thus, when DA synthesis is blocked by a-methyl- p-tyrosine (AMPT), the dose necessary for an antipsychotic effect is reduced (i.e., the dose-response curve is shifted to the left by the interaction between dopamine and AMPT). A drug such as reserpine that can deplete DA stores also has relatively mild antipsychotic properties. Also, aripiprazole, which has D 2 presynaptic agonist properties, decreases the production of DA, as well as blocking D2 postsynaptic receptors. 

Fig. 3. Locomotor hyperactivity to drugs activating forebrain dopamine systems (schematic illustration of response). A. Moderate doses of amphetamine induce progressive dose-dependent increases in counts recorded in automated activity chambers. B. At higher dose, amphetamine induces stereotypy which competes with the expression of locomotion resulting in a suppression of activity counts at peak dose. C. Competing stereotypy yields an inverse U function in the dose response curve (total activity over 2 h test). D. The dopamine receptor agonist apomorphine also increases activity at moderate doses which is blocked by competing stereotypy at high dose, but this drug also inhibits activity at the lowest doses, believed to be due to selective action at presynaptic autoreceptors (see text).

The agonists were found to vary considerably in their potency, with peak response in chlordimeform and XAMI treated insects occurring at 1 pg/g vs 100 pg/g for OA (Figure 2). The dose-response curves also show that males treated with chlordimeform, XAMI, lofexidine naphazoline, and synephrine exhibited levels of response to 0.01 mg pheromone that were equal to those of OA-treated (100 pg/g) males, but that clonidine, tolazoline, and tramazoline were much less effective, and that dopamine was without effect on male sensitivity. 

Figure 4. Dose-response curves of octopamine, tyramine, and dopamine in inhibiting specific f H] tyramine (3 nM) binding to the membranes of B96Bom/HEK-293 cells. Data represent means SD of at least two or three experiments, each done in duplicate. The specific to total binding ratio was 0.94 under the conditions used. The IC (fi of octopamine, tyramine, and dopamine were estimated to be 1.4 pM, 5.2 nM, and 1.7 pM, respectively. (Reproduced with permission from reference 9. Copyright 2003 Blackwell.)...

Venlafaxine and its active metabolite, 0-desmethylvenlafaxine (ODV), have dual mechanisms of action, with preferential affinity for 5-HT reuptake and weak inhibition of NE and dopamine reuptake. Venlafaxine is approximately 30 times more potent as an inhibitor of SERT than of NET (68). Because of the 30 times difference in transporter affinities, increasing the dose of venlafaxine from 75 to 375 mg/day can sequentially inhibit SERT and NERT. Thus, venlafaxine displays an ascending dose-dependent antidepressant response in contrast to the flat dose-antidepressant response curve observed with the SSRIs. This sequential action for venlafaxine also is consistent with its dose-dependent adverse-effect profile. Its mechanism of action is similar to imipramine. 

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