5- Hydroxytryptamine receptors/effects

Cheng, H.C., and Long, J.P. Effects of d- and /-amphetamine on 5-hydroxytryptamine receptors. Arch Int Pharmacodyn Ther 204 124-131, 1973. 

Leccese, A.R, Lyness, W.H. The effects of putative 5-hydroxytryptamine receptor active agents on D-amphetamine self-administration in controls and rats with 5,7-dihydroxytryptamine median forebrain bundle lesions. Brain Res. 303 153, 1984. 

Engleman EA, McBride WJ, Li TK, Lumeng L, Murphy JM (2003) Ethanol drinking experience attenuates (—)sulpiride-induced increases in extracellular dopamine levels in the nucleus ac-cumbens of alcohol-preferring (P) rats. Alcohol Clin Exp Res 27 424-31 Ennis C, Kemp JD, Cox B (1981) Characterisation of inhibitory 5-hydroxytryptamine receptors that modulate dopamine release in the striatum. J Neurochem 36 1515-20 Ensinger H, Majewski H, Hedler L, Starke K (1985) Neuronal and postjunctional components in the blood pressure effects of dopamine and bromocriptine in rabbits. J Pharmacol Exp Ther 234 681-90... 

Chaput Y, de Montigny C. Effects of the 5-hydroxytryptamine receptor antagonist BMY 7378, on 5-hydroxytryptamine neurotransmission electrophysiological studies in the rat central nervous system. J Pharmacol Exp Ther 1988 246 359-370. 

BW 723C86 is an indole-ethanamine, a selective (5-HT2B-subtype) S-hydroxytryptamine receptor agonist. It shows anxiolytic effects in an animal model, and is used as a pharmacological tool. 

Some derivatives of adamantane with antagonist or agonist effects have also been synthesized. For instance, monocationic and dicationic adamantane derivatives block the a-amino-3-hydroxy-5-methylisoxazole -propionic acid (AMPA) receptors, A-methyl-o-aspartate (NMDA) receptors [134—136] and 5-hydroxytryptamine (5-HT3) receptors [137]. 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

This hypothesis, similarly, proposes that physical activity increases tryptophan transport into the presynaptic neurone, where it is used to synthesise 5-hydroxytryptamine. Hence, when the nerve is stimulated, more 5-hydroxytryptamine is released into the synapse and, if this is another inhibitory transmitter in the motor control pathway, it will inhibit contraction (Figure 13.28). This is one of several effects of 5-hydroxytryptamine in the brain which are probably achieved via different receptors on different neurones. All three hypotheses are summarised in Figure 13.29. 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

McMahon, L. R. and Cunningham, K. A. 2001. Antagonism of 5-hydroxytryptamine 2A receptors attenuates the behavioral effects of cocaine in rats. Journal of Pharmacology and Experimental Theraphy, 297 357-363. 

Serotonin (5-hydroxytryptamine 5-HT) acts as transmitter and mediator on several locations in the body with quite different effects. There are multiple sub-types of the serotonin receptor. This offers the possibility of a selective therapeutic interference using subtype specific agonists or antagonists. 

Mayorga AJ, Dalvi A, Page ME, Zimov-Levinson S, Hen R, Lucki I (2001) Antidepressant-like behavioral effects in 5-hydroxytryptamine(lA) and 5-hydroxytryptamine(lB) receptor mutant mice. J Pharmacol Exp Ther 298 1101-1107 Mcllvain VA, Robertson DR, Maimone MM, McCasland JS (2003) Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels in neonatal GAP-43 heterozygous mice. J Comp Neiuol 462 252-264... 

The main effects of BZs occur via positive allosteric modulation. The BZs and GABA bind to separate sites on the GABAa receptor complex. When a BZ occupies the BZ receptor, GABA s ability to open the chloride channels increases. With greater opening of the chloride channel, cellular excitability decreases (Ballenger, 1995). The final result of this decreased cellular excitability is widespread because of the extensive inhibitory role of GABA in the CNS. As a result, BZs may alter the turnover of neurotransmitters such as norepinephrine and serotonin (5-hydroxytryptamine [5-HT]). 

Whitehouse PJ, Price DL, Clark AW, et al Alzheimer disease evidence for selective loss of cholinergic neurons in the nucleus basahs. Ann Neurol 10 122-126, 1981 Whitehouse PJ, Price DL, Struble RG, et al Alzheimer s disease and senile dementia—loss of neurons in the basal forebrain. Science 215 1237-1239, 1982 Whitehouse PJ, Hedreen JC, White CL, et al Basal forebrain neurons in dementia of Parkinson s disease. Ann Neurol 13 243-248, 1983 Whitehouse P, Martino A, Antuono P, et al Nicotinic acetylcholine binding sites in Alzheimer s disease. Brain Res 371 146-151, 1986 Whitehouse PJ, Martino AM, Marcus KA, et al Reductions in acetylcholine and nicotine binding in several degenerative diseases. Arch Neurol 45 722-724, 1988 Whitton PS, Sama GS, O Connell MT The effect of the novel antidepressant tianeptine on the concentration of 5-hydroxytryptamine in rat hippocampal diasylates in vivo. Neuropharmacology 39 1-4, 1991 Whitworth P, Kendall DA Lithium selectively inhibits muscarinic receptor-stimulated inositol tetrakisphosphate accumulation in mouse cerebral cortex slices. J Neurochem 51 258-265, 1988... 

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