5-Hydroxytryptamine properties

In assessing the anti-infl2immatory activity of phenothiazines, it should be emphasized that many of these substances possess potent anti-histamine and anti-5-hydroxytryptamine properties. They therefore have anti-inflammatory activity in those reactions produced by exogenous histamine or 5-hydroxytryptamine and in those in which either or both of these amines are liberated in situ, after injection of substances such as egg-white, dextran or compound 48/80 into the foot > . 

This accumulated evidence suggests that various phenothiazines can exert an anti-inflammatory effect which is unrelated to their antihistamine and anti-5-hydroxytryptamine properties. 

Chemistry and biological properties of polyfunctional indole-3-carbinol derivatives [l-(indol-3-yl)glycerols and related compounds, (3-hydroxytryptamines, and ascorbigens] 95F369. 

As an example, Fig. 17.4 presents the ligand efficiency of 107 compounds active against human 5-hydroxytryptamine lA receptor (data extracted from GVKBIO). Compounds A and B have different potencies (IC5oA= 12.2pM and IC5oB= 1.0 pM) and properties (MWA=244, HAA=18, CLOGPA=2.8 and MWB=294, HAB=22, CLOGPB = 4.1), but display a similar LE of 0.37. 

Combining molecular properties with potency provides a simple yet powerful overview of a screening dataset and can be used to quickly identify ligand-efficient lead-like compounds. In Fig. 17.5, a set of 429 compounds active against 5-hydroxytryptamine lA receptor are displayed in a PSA-ClogP plot with the size of the circle related to ligand efficiency. One can easily spot the efficient binders in area of favorable properties. 

Winter, J. C. (1978) Stimulus properties of phenethylamine hallucinogens and lysergic acid diethylamide The role of 5-hydroxytryptamine. J. Pharmacol. Exp. Ther., 204 416-423. 

The use of HPLC to analyze biogenic amines and their acid metabolites is well documented. HPLC assays for classical biogenic amines such as norepinephrine (NE), epinephrine (E), dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin) and their acid metabolites are based on several physicochemical properties that include a catechol moiety (aryl 1,2-dihydroxy), basicity, easily oxidized nature, and/or native fluorescence characteristics (Anderson, 1985). Based on these characteristics, various types of detector systems can be employed to assay low concentrations of these analytes in various matrices such as plasma, urine, cerebrospinal fluid (CSE), tissue, and dialysate. 

Peters JA, Garland JE, Cooper MA, Livesey MR, Deeb TZ, Hales TG, Lambert JJ (2006) Novel structural determinants of single-channel conductance in nicotinic acetylcholine and 5-hydroxytryptamine type-3 receptors. Biochem Soc Trans 34(5) 882-886 Picciotto MR, Zoli M, Rimondini R, Lena C, Marubio LM, Pich EM, Fuxe K, Changeux JP (1998) Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391 173-177... 

In Section 1.3, the general effects of fluorine substitution on drug activity and selectivity have been treated. As seen frequently with other enzymatic reactions, introduction of fluorine can have dramatic effects on the properties of substrates and inhibitors of MAOs [26]. For example, preliminary studies indicated that fluorination of 5-hydroxytryptamine in the 6- or the 4,6-positions (3,4) causes this predominantly MAO A substrate to be metabolized significantly by platelet MAO B [27]. Although no direct evidence was obtained, this may be caused by increased lipophilicity introduced by fluorine substitution. 

Mechanism of Action An antihypertensive that depletes stores of catecholamines and 5-hydroxytryptamine in many organs, including the brain and adrenal medulla. Depression of sympathetic nerve function results in a decreased heart rate and a lowering of arterial blood pressure. Depletion of catecholamines and 5-hydrox-ytryptamine from the brain is thought to be the mechanism of the sedative and tran-quilizing properties. Therapeutic Effects Decreases blood pressure and heart rate sedation. 

Meller E, Goldstein M, Geyer MA Receptor reserve for 5-hydroxytryptamine lA-mediated inhibition of serotonin synthesis possible relationship to anxiolytic properties of 5-hydroxitryptamine lA agonists. Mol Pharmacol 37 231-237, 1990... 

It is an alkaloid obtained from an African plant Yohimbehe. Chemically it is an indolealkylamine related to reserpine. It has selective blocking property with short duration of action and also blocks 5-hydroxytryptamine receptors. It produces increase in heart rate and blood pressure due to increase in noradrenaline release. It does not have any role in clinical practice. 

Blier P, Lista A de Montigny C. Differential properties of pre- and postsynaptic 5-hydroxytryptamine receptors in the dorsal raphe and hippocampus II.elfect of pertussis and cholera toxins. J Pharmacol Exp Ther 1993 265 16-23. 

Hadrava V, Blier P, Dennis T, Ortemann C de Montigny C. Characterization of 5-hydroxytryptamine(lA) properties of flesinoxan In vivo electrophysiology and hypothermia study. Neuropharmacology 1995 34 1311-1326. 

BIMU 1 is a benzimidazole-carboxamide derivative, a selective (S-HT -subtype) 5-hydroxytryptamine receptor AGONIST. It has antiemetic properties, and is used as a pharmacological tool. 

HYDROXYTRYPTAMINE RECEPTOR AGONIST that has PSYCHOTROPIC (hallucinogenic) properties, dimethoxystrychnine brucine, dimethyladamantanamine memantine, dimethylbiochanin B daidzein. P-dimethylcysteine penicillamine. 

BMY 13805-1 MJ 13805) is one of the azaspirone group structurally related to buspirone and with similar properties. It is a 5-hydroxytryptamine receptor agonist, a partial agonist at the 5HTi receptor subtype. It is a novel ANXIOLYTIC under investigation for treatment of anxiety and depression. 

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