5-Hydroxytryptamine receptors antidepressants

BIMU 8 is a benzimidazole-carboxamide derivative, a selective (5-HT4-subtype) 5-hydroxytryptamine receptor AGONIST. It has experimental GASTRIC motility stimulant (gastroprokinetic) activity used as a pharmacological tool, binedaline [inn] (Scha 1659) is a phenylindole, a noradrenaline uptake inhibitor and antidepressant. Never marketed. 

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... 

Froger N, Gardier AM, Moratalla R, Alberti I, Lena I, Boni C, De Felipe C, Rupniak NM, Hunt SP, Jacquot C, Hamon M, Lanfumey L (2001) 5-hydroxytryptamine (5-HT)lA autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization. J Neurosci 21 8188-8197 Gardier AM, Bourin M (2001) Appropriate use of knockout mice as models of depression or models of testing the efficacy of antidepressants. Psychopharmacology (Berl) 153 393-394... 

Nalepa I, Vetulani J Enhancement of the responsiveness of cortical adrenergic receptors by chronic administration of the 5-hydroxytryptamine uptake inhibitor citalopram. J Neurochem 60 2029-2035, 1993 Nalepa I, Vetulani J The responsiveness of cerebral cortical adrenergic receptors after chronic administration of atypical antidepressant mianserin. J Psychiatry Neurosci 19 (2) 120, 1994... 

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... 

Consolo S, Wu CF, Fusi R (1987) Di receptor-linked mechanism modulates cholinergic neurotransmission in rat striatum. J Pharmacol Exp Ther 242 300-5 Consolo S, Arnaboldi S, Giorgi S, Russi G, Ladinsky H (1994) 5-HT4 receptor stimulation facilitates acetylcholine release in rat frontal cortex. Neuroreport 5 1230-2 Cooper AJ, Stanford IM (2001) Dopamine D2 receptor mediated presynaptic inhibition of stri-atopallidal GABAa IPSCs in vitro. Neuropharmacol 41 62-71 Cox B, Kerwin RW, Lee TF, Pycock CJ (1980) A dopamine-5-hydroxytryptamine link in the hypothalamic pathways which mediate heat loss in the rat. J Physiol 303 9-21 Dailly E, Chenu F, Renard CE, Bourin M (2004) Dopamine, depression and antidepressants. Fun-dam Clin Pharmacol 18 601-7... 

Serotonin plays an active role in temperature regulation and in particular in the maintenance of the body s set point [543-545]. More recently, numerous pharmacological studies have suggested the involvement of homeostatic control mechanisms [544, 546] that are achieved through interplay between the 5-hydroxytryptamine (HT)1A and 5-HT2A/C receptor systems [545,547,548]. Administration of a 5-HTlA-receptor agonist that is used therapeutically as an antidepressant and antianxiety drug causes hypothermia [549,550]. 

There is a great deal of evidence that deficiency of serotonin (5-hydroxytryptamine) is a factor in depressive illness, and many antidepressant drugs act to decrease its catabolism or enhance its interaction with receptors. A key enzyme involved in the synthesis of serotonin (and the catecholamines) is aromatic amino acid decarboxylase, which is pyridoxal phosphate-dependent. Therefore, it has been suggested that vitamin Be deficiency may result in reduced formation of the neurotransmitters and thus be a factor in the etiology of depression. Conversely, it has been suggested that supplements of vitamin Be may increase aromatic amino acid decarboxylase activity, and increase amine synthesis and have a mood-elevating or antidepressant effect. There is little evidence that vitamin Be deficiency affects the activity of aromatic amino acid decarboxylase. In patients with kidney failure, undergoing renal dialysis, the brain concentration of pyridoxal phosphate falls to about 50% of normal, with no effect on serotonin, catecholamines, or their metabolites (Perry etal., 1985). 

Most antidepressants in clinical use today act by enhancing the neurotransmission of serotonin [5-hydroxytryptamine (5-HT)], norepinephrine [NE noradrenaline (NA)], or both. They do so either by blocking the reuptake (transport) of neurotransmitter, blocking the metabolism of neurotransmitter [i.e., monoamine oxidase (MAO) inhibitors], or by direct action on a neurotransmitter receptor. Hence, the antidepressants can be classified on the basis of their putative mechanisms of action (Table 8.2 and Figs. 8.1-8.4). Agents that block neurotransmitter reuptake can be further divided into those that are non-selective (e.g., tricyclic antidepressants with mixed action), serotonin-selective reuptake... 

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