Autoreceptors serotonin

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

Langer, S. Z., and Moret, C. (1982) Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus. J. 

LSD AND SEROTONERGIC DORSAL RAPHE NEURONS LSD and Serotonin Autoreceptors... 

In the following paragraphs, we examine bioactive cyclic imides substituted on the ring and/or on the N-atoms, and begin with N-substituted suc-cinimides. CP-93,393 (4.177, R=R =H) is a selective 5-HT, serotonin autoreceptor agonist developed for the treatment of anxiety and depression. In the rat, hydrolysis of the succinimide bond was observed for the parent drug as well as for metabolites hydroxylated on the succinimide ring (4.177, R=OH,... 

Serotonin 5-HT1A Human cDNA Alzheimer s disease, anxiety, depression, schizophrenia, hypertension, inflammation, pain, migraine, spasticity ulcers, obesity glaucoma Somatodendritic autoreceptor in hippocampus and raphe nuclei, circadian rhythm, somatodendritic heteroreceptor at cholinergic terminals of myenteric plexus... 

Lappalainen, J., Dean, M., Charbonneau, L., Virkkunen, M., LinnoUa, M., and Goldman, D. (1995) Mapping of the serotonin 5-HTlD beta autoreceptor gene on chromosome 6 and direct analysis for sequence variants. Am. J. Med. Genet. 60, 157-161. 

Pindolol (Visken). A beta blocker known to potentiate serotonin activity via a distinct action on serotonin autoreceptors, pindolol has been reported in a controlled study to augment SSRl treatment in OCD patients who are partial responders. Pindolol is administered at a dose of 2.5 mg three times daily. It is generally well tolerated but low blood pressure, dizziness, and sedation can occur. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

These drugs increase synaptic serotonin by selectively blocking the serotonin reuptake transporter. In preclinical and human studies acute doses tend to be anxiogenic (Bell and Nutt 1998) but chronic administration has anxiolytic effects, possibly due to downregulation of presynaptic autoreceptors (Blier et al. 1990). There are five SSRIs widely available citalopram, fluoxetine, fluvoxam-ine, paroxetine and sertraline. Escitalopram, the S-enantiomer of citalopram. 

A recent positron emission tomography (PET) study in which the radiolabeled serotonin precursor alpha C methyl tryptophan was used provides empirical evidence of decreased 5-HT synthesis in frontal and thalamic regions and increased 5-HT synthesis in contralateral cerebellar dentate regions (Chugani et al., 1997). These findings are consistent with findings of increased 5-HTm inhibitory autoreceptor sensitivity in adult autistic patients (Hollander et al., 2000 Novotny et al., 2000), since these receptors are prevalent in frontal and thalamic, but not cerebellar, regions. 

Tricyclic antidepressants bind presynaptically to the 5-HTi autoreceptor site, leading to decreased serotonin reuptake and degradation. Postsynaptically TCAs bind to 5-HT2 receptors, leading to increased activity. 

Imipramine Tertiary Blockade of norepinephrine reuptake at 0.2 autoreceptor and blockade of serotonin reuptake at 5-HTi autoreceptor 13 2 42 2 Enuresis, age 6+ years... 

Some authors (Flament et ah, 1987) found that response to treatment with clomipramine was correlated with a marked decrease in platelet serotonin concentration and monoamine oxidase (MAO) activity. Changes in cerebrospinal fluid (CSF) neuropeptides and monoamine metabolites have also been described with chronic clomipramine administration (Swedo et ah, 1992 Altemus et ah, 1994). Despite these observations, the exact mechanism of action of serotonergic drugs (and the serotonin hypothesis ) remains unproven, although it is thought they mediate their effects via down-regulation of the presynaptic 5-HTlD autoreceptor (Rauch et ah, 1994). 

It is thought that some problems with brain functioning might be due to breakdowns in this autoreceptor feedback system. Both norepinephrine and serotonin have autoreceptor feedback systems in the nuclei in which the cells originate. These systems appear to be affected in some models of anxiety. 

Although postsynaptic DA agonists and presynaptic Dj autoreceptor antagonists share a common property of enhancing DA transmission, Dj autoreceptor agonists have been developed specifically to block DA transmission as an alternative approach to antipsychotic therapy (Benkert et al. 1992). A variety of such compounds are available (Seyfried and Boettcher 1990), four of which—talipexole, pramipexole, roxindole, and OPC-4392 —have been evaluated as antipsychotics in schizophrenic patients (Benkert et al. 1992). Only roxindole has been tested in depression, and then only in two uncontrolled pilot studies over 4 weeks of treatment (Benkert et al. 1992 M. Kellner et al. 1994). Response rates similar to those of imipramine were observed, with a fast onset of action in some patients. Roxindole s antidepressant action may lie in its ability to selectively stimulate supersensitive postsynaptic Dj receptors, and thereby enhance DA function, or in its additional properties as an inhibitor of serotonin reuptake and as a 5-HT, receptor agonist (Benkert et al. 1992 Seyfried et al. 1989). 

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