Serotonin inhibition

Monoaminooxidase is a complex enzymatic system that is present in practically every organ that catalyzes deamination or inactivation of various natural, biogenic amines, in particular norepinephrine (noradrenaline), epinephrine (adrenaline), and serotonin. Inhibition of MAO increases the quantity of these biogenic amines in nerve endings. MAO inhibitors increase the intercellular concentration of endogenous amines by inhibiting then-deamination, which seems to be the cause of their antidepressant action. 

In fact, the SSRI-RBD link sounds a lot like the Thorazine-tardive dyskinesia tie-in, doesn t it What possibly common underlying mechanism could unite these apparently disparate phenomena One answer is dopamine, whose production by the substantia nigra is deficient in spontaneous Parkinsonism. Dopamine is blocked, hence rendered functionally deficient, by the antipsychotics that produce both immediate and delayed Parkinsonian side effects. Serotonin inhibits dopamine, which means that potentiating serotonin with SSRIs could also render dopamine less functionally efficacious. Acetylcholine is in dynamic reciprocity with both serotonin and dopamine. Acetycholine causes an increase in dopamine s efficacy in some circuits and a decrease in others. 

Serotonin has important influences on dopamine, but that influence is quite different in each of the four dopamine pathways. Understanding the differential serotonergic control of dopamine release in each of these four pathways is critical to understanding the differential actions of antipsychotic drugs that block only dopamine 2 receptors (i.e., the conventional antipsychotics) versus antipsychotic drugs that block both serotonin 2A and dopamine 2 receptors (i.e., the atypical antipsychotics). That is, serotonin inhibits dopamine release from dopaminergic axon terminals in the various dopamine pathways, but the degree of control differs from one dopamine pathway to another. 

FIGURE 11—17. Serotonin-dopamine interactions in the nigrostriatal dopamine pathway. Serotonin inhibits dopamine release, both at the level of dopamine cell bodies in the brainstem substantia nigra and at the level of the axon terminals in the basal ganglia—neostriatum (see also Figs. 11 — 18 through 11 —20). In both cases, the release of serotonin acts as a brake on dopamine release. 

Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Aihara H (1988b) Serotonin-2 receptor-mediated regulation of release of acetylcholine by minaprine in cholinergic nerve terminal of hippocampus of rat. Neuropharmacology 27 603-9 Muramatsu M, Lapiz MD, Tanaka E, Grenhoff J (1998) Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5-HTjb receptors. Eur J Neurosci 10 2371-9... 

Maura G, Marcoli M, Pepicelli O, Rosu C, Viola C, Raiteri M. Serotonin inhibition of the NMDA receptor/nitric oxide/cyclic GMP pathway in human neocortex slices involvement of 5-HT2c and 5-HT1A receptors. Br J Pharmacol 2000 130 1853-1858. 

Gill RK, Saksena S, Tyagi S, et al. Serotonin inhibits Na+/H+ exchange activity via 5-HT4 receptors and activation of PKCa in human intestinal epithelial cells. Gastroenterology 2005 128 962-974. 

Del Mar LP, Cardenas CG, Scroggs RS. Serotonin inhibits high-threshold Ca2+ channel currents in capsaicin-sensitive acutely isolated adult rat DRG neurons. J Neurophysiol 1994 72 2551-2554. 

Herness S, Chen Y. 1997. Serotonin inhibits calcium-activated K current in rat taste receptor cells. Neuroreport 8 3257-3261. 

Edagawa Y, Saito H, Abe K (1998a) Serotonin inhibits the induction of long-term potentiation in rat primary visual cortex. Prog Neuropsycholopharmacol Biol Psychiatry 22 983-997. 

Reuptake of serotonin inhibited by SSRIs, TCAs, trazodone, nefazodone... 

Monoamine oxidase is an enzyme that metabolizes monoamines. MAO-B is more specific for dopamine, than for noradrenaline or serotonin. Inhibition of MAO-B slows the breakdown of dopamine thereby increasing its availability at synapses and prolonging its effects. 

Serotonin inhibits the enzyme superoxide dismutase, which protects cells against oxidative damage (by radicals ) that leads to the death of the cell due to its chemical degradation. 

The antidepressant activity of hypericum has been extensively investigated over the last two decades in animal models (forced-swimming and tail-suspension tests) as well as in humans. Clinical trials have demonstrated an improvement in symptoms of anxiety, dysphoric mood, hypersomnia, anorexia, depression, insomnia, psychomotor retardation, and other subjective indicators.Potential for the treatment of premenstrual syndrome (PMS) also exists. Earlier studies also showed that hypericum enhanced mice exploratory activity in a foreign environment, extended narcotic sleeping time (dose dependent), is a reserpine antagonist, and decreased aggression in socially isolated male mice. Hypericin has been found to inhibit in vitro almost irreversibly both type A and B monoamine oxidase (MAO) in rat brain mitochondria. Type A MAO (serotonin) inhibition was more pronounced, but with long-term use (8 weeks of daily treatment). Other mechanisms of action, such as serotonin transport and up-... 

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