HT-1479

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

In addition to H2, D2, and molecular tritium [100028-17-8] the following isotopic mixtures exist HD [13983-20-5] HT [14885-60-0] and DT [14885-61-1]. Table 5 Hsts the vapor pressures of normal H2, D2, and T2 at the respective boiling points and triple points. As the molecular weight of the isotope increases, the triple point and boiling point temperatures also increase. Other physical constants also differ for the heavy isotopes. A 98% ortho—25/q deuterium mixture (the low temperature form) has the following critical properties = 1.650 MPa(16.28 atm), = 38.26 K, 17 = 60.3 cm/mol3... 

Melatonin. Melatonin (A/-acetyl-5-metlioxytryptaniine) [73-31-4] C 2H gN2O2(250) is secreted from the pineal gland and retina during dark periods of the vertebrate circadian rhythm (65). Melatonin regulates biological rhythms and neuroendocrine function and is formed from serotonin (5-HT). 

Serotonin. Seiotonin [50-67-9] (5-HT), (287) is a hydioxyethylaminoindole with widespread distribution. 5-HT is synthesized from... 

L-tryptophan by hydroxylation to 5-hydroxy-L-tryptophan by the enzyme, ttyptophan-5-hydroxylase. 5-Hydroxy-L-tryptophan is then rapidly decarboxylated by aromatic-L-amino acid deacarboxylase to 5-HT. The actions of 5-HT as a neurottansmitter ate terminated by neuronal reuptake and metabobsm. 

DOI (294) and a-methyl-5-HT (295) are selective 5-HT2 receptor agonists. Ketansetin (296) and ritansetin (297) are potent and selective 5-HT2 antagonists. SB 200646 (298) is an antagonist which has greater selectivity toward 5-HT2g and receptors compared to the 5-HT2 subtype. 

Whereas the agreement between the values in humans and guinea pig is close, this is not always so. For example, in human and rodent 5-HT p receptors, significant pharmacological differences are conferred by a single amino acid residue. 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

More interesting is the mechanism of action of atypical antipsychotics, particularly clo2apine (60). It is also probably the least selective antipsychotic used in the clinic, having high affinity for numerous receptors including 5-HT2, 5-HT, and dopamine D, D3) and receptors ... 

It has been suggested that high affinity for certain 5-HT receptors is a possible method for reducing extrapyramidal side effects observed with antipsychotics. LiabiUty for extrapyramidal side effects has been hypothesi2ed to be related to the ratio of the affinity between dopamine receptor... 

HT, after chronic adininistration of all clinically effective antidepressants and after electroconvulsive treatment. A detailed review of the neuropharmacology of antidepressants is available (30). 

Serotoninergic neurons utilize serotonin [50-67-9] 5-hydroxy-tyrptamine (5-HT), as a neurotransmitter. Central serotoninergic... 

Table A16.5 HT Cables up to 11 kV Armoured three-core power cables 1.9/3.3 kV ...

Reaction of tetrahydroquinoline 257 with ethyl bromopyruvate afforded pyrroloquinoline 260 which upon transesterification by treatment with tropine in presence of sodium methoxide in toluene gave 261 which was found to be useful as 5-HT receptor antagonist (89EP322016). 

Serotonin agonists G-protein coupled 5-HT receptors 5-HT3 ion channels cAMP (5-HT-,) t cAMP (5-HT4 7) t PLC (5-HT2) l Release of excitatory neuropeptides l Neurogenic inflammation f vasoconstriction Myocardial infarction, stroke, peripheral vascular occlusion... 

Antidepressants Noradrenaline/5-HT transporters Na+, K+ channels l Noradrenaline/ 5-HT reuptake l Na+ currents t K+ currents l Excitability of peripheral and central neurons Cardiac arrhythmia, myocardial infarction, sedation, nausea, dry mouth, constipation, dizziness, sleep disturbance, blurred vision... 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

---