Dopamine dosing

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

COMT inhibitors rescue l-dopa and improve the brain entry of L-dopa by decreasing 3-OMD formation in peripheral tissues. The dose of L-dopa could be decreased, compared with the present combination therapy. Dose interval of L-dopa could also be prolonged. Further, COMT inhibitors should decrease fluctuations of dopamine formation in the brain. 

At low doses, both psychostimulants could theoretically stimulate tonic, extracellular levels of monoamines, and the small increase in steady state levels would produce feedback inhibition of further release by stimulating presynaptic autoreceptors. While this mechanism is clearly an important one for the normal regulation of monoamine neurotransmission, there is no direct evidence to support the notion that the doses used clinically to treat ADHD are low enough to have primarily presynaptic effects. However, alterations in phasic dopamine release could produce net reductions in dopamine release under putatively altered tonic dopaminergic conditions that might occur in ADHD and that might explain the beneficial effects of methylphenidate in ADHD. 

A simple decrease in striatal dopamine transmission produced by even low clinical doses of the dtugs according to current data seems an untenable... 

L-DOPA/Levodopa Dopa Decarboxylase Dopamine System Dopamine- 3-hydroxylase Dopaminergic Neurotoxicity Dose... 

There are few reports on the effects of nitrous oxide on dopaminergic neurotransmission. A study in mice showed that nitrous oxide inhalation produced a significant increase in locomotor activity that was antagonized in a dose-dependent fashion by the dopamine synthesis inhibitor a-methyl-/)-tyrosine (Hynes and Berkowitz 1983). Moreover, administration of the D2 antagonist haloperidol also reduced the locomotor activity induced by nitrous oxide (Hynes and Berkowitz 1983). These results suggest that excitatory effects induced by nitrous oxide may be also mediated by dopaminergic neurotransmission. However, other studies have reported that exposure to nitrous oxide resulted in decreased dopamine release by neurons in the striatum (Balon et al. 2002 Turle et al. 1998). 

Hillefors-Berglund M, Liu Y, von Euler G Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen. Toxicology 77 223-232, 1993... 

Bellomo R. Chapman M, Finfer S, Hickhng K, Myburth J Low-dose dopamine in patients with early renal dysfunction a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Chnical Trials Group. Lancet 2000 356 2139-2143. 

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

The first proper double blind trial of embryonic implants in 40 PD patients (20 undergoing just surgery without any implant), has shown no improvement in patients over 60 years but some clinical benefit (fewer symptoms between levodopa dosing) in those below that age. Unfortunately some of these responders eventually developed dyskinesias, a sign of too much dopamine, and further implants were halted until the technique has been re-evaluated, see Freed, CR et al. N EnglJ Med 2001, 344 710-719. 

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