5-Hydroxytryptamine pharmacology

Dennis J. McKenna, X.-M. Guan, and A. T. Shulgin. "3,4-methyl-enedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine." Pharmacology, Biochemistry, and Behavior 38 (1991) 505-12. 

Hoyer D, Clarke DE, Fozard JR et al (1994) International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev 46 157-204... 

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. 

In view of this neurotoxicity, we will review some data relevant to this process. First, we will review data showing that methamphetamine (METH), a prototypic psychomotor stimulant, which has been widely used for nonmedical purposes at doses often a good deal higher than therapeutie doses, is neurotoxic to dopamine (DA) and serotonin (5-hydroxytryptamine (5-HI)) systems. Second, we will examine the evidence that other substituted phenethylamines are also neurotoxic to certain transmitter systems. Last, we will examine the behavioral and pharmacological consequences of neurotoxicity that result from exposure to some of these amphetamine-related drugs. 

Ko FN, Yu SM, Su MJ, Wu YC, Teng CM. Pharmacological activity of (-)-discreta-mine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens. BrJ Pharmacol. 1993 110 882-888. 

Neurochemical theories for the affective disorders propose that there is a link between dysfunctional monoaminergic synapses within the central nervous system (CNS) and mood problems. The original focus was the neurotransmitter noradrenaline, or NA (note noradrenaline is called norepinephrine, or NE, in American texts). Schildkraut (1965) suggested that depression was associated with an absolute or relative deficiency of NA, while mania was associated with a functional excess of NA. Subsequently, another monoamine neurotransmitter 5-hydroxytryptamine (5-HT), or serotonin, was put forward in a rival indoleamine theory (Chapter 2). However, it was soon recognised that both proposals could be reconciled with the available clinical biochemical and pharmacological evidence (Luchins, 1976 Green and Costain, 1979). 

Deraet, M., Manivet, P., Janoshazi, A., Callebert, J., Guenther, S., Drouet, L., Launay, J.M. and Maroteaux, L. (2005) The natural mutation encoding a C terminus-truncated 5-hydroxytryptamine 2B receptor is a gain of proliferative functions. Molecular Pharmacology, 67 (4), 983-991. 

Another proposed mechanism of byssinosis is pharmacologic mediator release, especially histamine and 5-hydroxytryptamine (5-HT). Studies of histamine release following cotton dust exposure are complicated by the fact that cotton Itself contains histamine (98), the majority of which is found in the dust particle fraction below 20 P size (99). 

Hoyer D, Qarke DE, Eozard JR, et al. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 1994 46 157-203. 

Pharmacology Naratriptan, rizatriptan, sumatriptan, frovatriptan, almotriptan, eletriptan, and zolmitriptan are selective agonists for a vascular 5-hydroxytryptamine-i(serotonin) receptor subtype. Use of 5-HT- agonists results in... 

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. 

PHARMACOLOGICAL ACTIVITIES AND CLINICAL TRIALS 5-Hydroxytryptamine inhibition. Ethanol (80%) extract of the dried stem hark, in cell culture at a dose of 10 pg/mL, inhibited the uptake of serotonin (5HT) in rat brainstem neurons L... 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

Boden PR, Woodruff GN, Pinnock RD Pharmacology of a cholecystokinin receptor on 5-hydroxytryptamine neurons in dorsal raphe of the rat. Br J Pharmacol 102 635-638, 1991... 

Serotonin (4.109, 5-hydroxytryptamine, 5-HT) is a central neurotransmitter that is also found peripherally in the intestinal mucosa and in blood platelets, where its role is incompletely elucidated it even occurs in plants such as bananas. Although there is an enormous literature on the biochemistry and pharmacology of serotonin, our knowledge of its biological role remains somewhat fragmented. The diverse physiological effects of 5-HT influence the cardiovascular system, the cerebrovascular system, the digestive... 

Mansour, T.E. (1957) The effect of lysergic acid diethylamide, 5-hydroxytryptamine and related compounds on the liver fluke Fasciola hepatica. British journal of Pharmacology 12, 406-409. 

Baumgarten, H. G. and Goethert, M. (Eds) Serotoninergic neurons and 5-hydroxytryptamine receptors in the CNS. Handbook of Experimental Pharmacology, Vol. 129. Berlin Springer-Verlag, 1997. 

Lopez-Rodriguez ML, Vicente B, Deupi X, et al. Design, synthesis and pharmacological evaluation of 5-hydroxytryptamine(la) receptor ligands to explore the three-dimensional structure of the receptor. Mol Pharmacol 2002 62 15-21. 

Hirst WD, Abrahamsen B, Blaney FE, et al. Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol Pharmacol 2003 64 1295-1308. 

Ireland SJ, Tyers MB. Pharmacological characterization of 5-hydroxytryptamine-induced depolarization of the rat isolated vagus nerve. Br J Pharmacol 1987 90 229-238. 

Shenker A, Maayani S, Weinstein H, Green JP. Pharmacological characterization of two 5-hydroxytryptamine receptors coupled to adenylate cyclase in guinea pig hippocampal membranes. Mol Pharmacol 1987 31 357-367. 

Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R. Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus. J Neurochem 1998 70 2252-2261. 

The first of at least 14 serotonin (5-hydroxytryptamine [5-HT]) receptor types currently known to exist in the mammalian central nervous system (CNS) was pharmacologically defined more than 25 yr ago (1,2). Yet, it is only within the last 15 yr, with the cloning and sequencing of these receptors, that it has become possible to visualize their distribution at cellular and subcellular... 

---