Dopamine inhibitor-induced

Methylphenidate like cocaine largely acts by blocking reuptake of monoamines into the presynaptic terminal. Methylphenidate administration produces an increase in the steady-state (tonic) levels of monoamines within the synaptic cleft. Thus, DAT inhibitors, such as methylphenidate, increase extracellular levels of monoamines. In contrast, they decrease the concentrations of the monoamine metabolites that depend upon monoamine oxidase (MAO), that is, HVA, but not catecholamine-o-methyltransferase (COMT), because reuptake by the transporter is required for the formation of these metabolites. By stimulating presynaptic autoreceptors, methylphenidate induced increase in dopamine transmission can also reduce monoamine synthesis, inhibit monoamine neuron firing and reduce subsequent phasic dopamine release. 

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). 

Synergy of unwanted pharmacological effect ginseng and its products will inhibit the central nervous system (CNS) when they are applied with luminal, chloral hydrate, or ephedrine, which can increase the release of dopamine, noradrenaline, and serotonin in the CNS thus inducing a hypertensive crisis if monoamine oxidase inhibitors (MAOIs) are given simultaneously. 

Hanania, T. and Zahniser, N.R., Locomotor activity induced by noncompetitive NMDA receptor antagonists versus dopamine transporter inhibitors opposite strain differences in inbred long-sleep and short-sleep mice, Alcohol Clin. Exp. Res., 26, 431, 2002. 

Nash, J.F. and Brodkin, J., Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release effect of dopamine uptake inhibitors, J. Pharmacol. Exp. Ther. 259(2), 820-825, 1991. 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

Nolen WA, Haffmans PMJ, Bouvy PF, et al Monoamine oxidase inhibitors in resistant major depression. J Affect Disord 28 189-197, 1993 Nomikos GC, Damsma G, Wenkstern D, et al Chronic desipramine enhances amphetamine-induced increases in interstitial concentrations of dopamine in the nucleus accumbens. Eur J Pharmacol 195 63-73, 1991 Nomikos GC, Damsma D, Wenkstern D, et al Effects of chronic bupropion on interstitial concentrations of dopamine in rat nucleus accumbens and striatum. Neuropsychopharmacology 7 7-14, 1992... 

Many inhibitors of the amine transporters for norepinephrine, dopamine, and serotonin are used clinically. Although specificity is not absolute, some are highly selective for one of the transporters. Many antidepressants, particularly the older tricyclic antidepressants can inhibit norepinephrine and serotonin reuptake to different degrees. This may lead to orthostatic tachycardia as a side effect. Some antidepressants of this class, particularly imipramine, can induce orthostatic hypotension presumably by their clonidine-like effect or by blocking 04 receptors, but the mechanism remains unclear. 

In addition to MPTP, other endogenously produced neurotoxins, namely, the monoamine-derived 1,2,3,4-tetrahydroisoquinolines and 6,7-dihydroxy-l,2,3,4-tetrahydroisoquinolines, have been proposed as factors accelerating dopamine cell death. A-methylated isoquinolines were found to be oxidized by MAO, and hydroxyl radicals were found to be produced by this reaction. In addition, by incubation with the A-methylated isoquinolines, ATP was depleted from a dopaminergic cell model. Pretreatment of the cells with MAO inhibitors such as selegiline could, however, protect against ATP depletion. These results suggest that oxidation of neurotoxic isoquinolines is directly involved in the oxidative stress to induce the cell death of dopamine neurons. On the other hand, 1 -methyl-1,2,3,4-tetrahydroisoquinoline and 1 -methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquino-... 

Protection was not associated with MAO-B inhibition in that pargyline, a potent MAO inhibitor, was ineffective and pretreatment with pargyline did not prevent the protective effects of selegiline. Protection was not associated with inhibition of dopamine uptake by selegiline because the dopamine uptake inhibitor mazindol did not diminish BSO toxicity. Antioxidant ascorbic acid (200 iM) also protected BSO-induced cell death, suggesting that oxidative events were involved. This... 

The dopamine-stimulated formation of cAMP may initiate the dopamine-induced release of IR-PTH. A linear relationship exists between the dopamine-induced release of IR-PTH and the logarithm of the dopamine-induced accumulation of cAMP (17). Similarly, other agents increasing cAMP accumulation and IR-PTH release (e.g. beta-adrenergic agonists, secretin and phosphodiesterase inhibitors, also display such a log-linear relationship. Additional support for the possibility that intracellular cAMP might initiate PTH secretion comes from the observations that cholera toxin (JJ.), phosphodiesterase inhibitors (17) and dibutyryl cAMP (18), agents known to increase intracellular cAMP or mimic the biochemical effects of cAMP, increase the release of IR-PTH. 

As illustrated in Fig. 3A, dopamine leads to a 30% (p <0.01) inhibition of basal cyclic AMP levels in pars intermedia cells at an EDgg value of 5.0 nM. An almost identical potency of dopamine is observed on the elevated cyclic AMP concentration induced by simultaneous incubation with 30 nM (-)isoproterenol (Fig. 3B). Similar inhibitory effects of dopamine are observed in the presence of a phosphodiesterase inhibitor, isobutylmethylxanthine, thus... 

Cessation of impulse flow in dopaminergic neurons can be achieved by administration of gammabutyrolactone (GBL). In the presence of a dopa decarboxylase inhibitor this induces an accumulation of DOPA. Administration of dopamine receptor agonists decreases this accumulation of DOPA, an affect which can be antagonized by pretreatment with neuroleptics (recently reviewed by Roth, 109). 

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