Serotonin 5-HT

Melatonin. Melatonin (A/-acetyl-5-metlioxytryptaniine) [73-31-4] C 2H gN2O2(250) is secreted from the pineal gland and retina during dark periods of the vertebrate circadian rhythm (65). Melatonin regulates biological rhythms and neuroendocrine function and is formed from serotonin (5-HT). 

Trace amines are a family of endogenous monoamine compounds including (3-phenylethylamine (PEA), p-tyramine (TYR), tryptamine (TRP) and octopamine (OCT). The trace amines share close structural similarity with the well known classical monoamine neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-HT). As their name suggests, trace amines occur in comparably much lower abundance than monoamine neurotransmitters. For historical reasons, other endogenous amine compounds which might share some structural similarities with PEA, TYR, TRP or OCT are not referred to as trace amines. 

Arylpiperazines have immensely important effects on various and diverse biological targets, in particular on CNS receptors. In the case of serotonin (5-HT) receptors, compounds containing this arylpiperazine moiety represent the largest systematically studied class of 5-HTia receptor ligands [63]. Structural alterations within long-chain arylpiperazines (LCAPs) occur mainly at the two opposite ends of a molecule and have been described by many authors [64-71]. 

FIGURE 1. The effect of repeated systemic administration of various doses of MDMA on the content of serotonin (5-HT) and S-HIAA and the density of 5-HT uptake sites in rat frontal cerebral cortex... 

MDMA, MDMA plus 10 mg/kg citalopram, and MDMA plus 25 mg/kg SKF 525A on the density of serotonin (5-HT) uptake sites in homogenates of rat frontal cerebral cortex... 

FIGURE 5. Timecourse of recovery of (A.) serotonin (5-HT) uptake sites and (B.) 5-HT conten in rat cerebral cortex following repeated systemic administration of MDMA... 

NOTE Comparison of the affinities (K1 values) of amphetamine derivates at serotonin(5-HT)... 

Serotonin (5-HT)-tenninal autoreceptor antagonists, 41 (2003) 129 Single photon emission tomography (SPET), 38 (2001) 189... 

The organ also contains neuroactive compounds as constituents of the vasomotor and neuro-glandular tissues (Zancanaro et al., 1997). These include the amine transmitters Nor-adrenalin and Serotonin (5-HT), whose presence is presumably related to the non-olfactory innervations. Local stimulation effects [Figs. 5.2 and 5.5(a)] can alter the biogenic amine levels in the VNO of female mice, as a result of exposure to male conspecific urine, and consequent arousal of the suction-pump [c.f. Fig. 5.7(a)]. 

O Classic views as to the cause of major depressive disorder focus on the monoamine neurotransmitters norepinephrine (NE), serotonin (5-HT), and to a lesser extent, dopamine (DA) in terms of both synaptic concentrations and receptor functioning. 

Masellis, M., Basile, V. S., Meltzer, H. Y. etal. (2001). Lack of association between theT->C 267 serotonin 5-HT 6 receptor gene (HTR6) polymorphism andprediction of response to clozapine in schizophrenia. Schizophr. Res., 15, 49-58. 

Figure 2.4 Flip-flop switch model of wake and slow wave sleep active systems. Mutually inhibitory connections exist between GABAergic/Galaninergic slow wave sleep active neurons in the ventrolateral preoptic area (VLPO) of the anterior hypothalamus and aminergic neurons in the hypothalamus (histamine (HA) neurons in the tuberomammillary nucleus (TMN)) and brainstem (serotonin (5-HT) neurons in the dorsal raphe (DR) and noradrenaline (NA) neurons in the locus coeruleus (LC)). Orexinergic neurons in the perifornical hypothalamus (PFH) stabilize the waking state via excitation of the waking side of the flip-flop switch (aminergic neurons).

Liu, R., Jolas, T. Aghajanian, G. (2000). Serotonin 5-HT(2) receptors activate local GABA inhibitory inputs to serotonergic neurons of the dorsal raphe nucleus. Brain Res. 873, 34-45. 

The neural structures involved in the promotion of the waking (W) state are located in the (1) brainstem [dorsal raphe nucleus (DRN), median raphe nucleus (MRN), locus coeruleus (LC), laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), and medial-pontine reticular formation (mPRF)] (2) hypothalamus [tuberomammillary nucleus (TMN) and lateral hypothalamus (LH)[ (3) basal forebrain (BFB) (medial septal area, nucleus basalis of Meynert) and (4) midbrain ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (Pace-Schott Hobson, 2002 Jones, 2003). The following neurotransmitters function to promote W (1) acetylcholine (ACh LDT/PPT, BFB) (2) noradrenaline (NA LC) (3) serotonin (5-HT DRN, MRN) (4) histamine (HA TMN) (5) glutamate (GLU mPRF, BFB, thalamus) (6) orexin (OX LH) and (7) dopamine (DA VTA, SNc) (Zoltoski et al, 1999 Monti, 2004). 

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

MAOI non-selective monoamine oxidase (A/B) inhibitors RIMA reversible inhibitor of monamine oxidase type A SSRI selective serotonin (5-HT) reuptake inhibitors SNRI serotonin/noradrenaline reuptake inhibitor SNARI selective noradrenaline (NA) reuptake inhibitor NA = 5-HT — DA potency of the drug is very similar in raising the level of both (or all three) monamines NA > 5-HT more selective for NA 5-HT>NA more selective for 5-HT NA increases the release of NA. 

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