Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychotherapeutic and pharmacological treatment of bulimia and vomiting require long duration and frequently entail considerable obstacles in patience compliance, making such regimens difficult to pursue. The regulating mechanism of the appetite center is recognized to be complex and recently an important role of serotonin (5-HT), a neurotransmitter, has been shown in rats. In the present study a newly developed 5-HT1A agonist, SM-3997, was administered to 12 patients with bulimia and its clinical efficacy was evaluated. The patients were treated on an open basis with SM-3997, 30-40 mg/day, for 6-15 weeks. Bulimic behavior stopped completely in 4 patients, was improved in 4 others and was unchanged in the remaining 4. These results suggest that the administration of a 5-HT1A agonist, SM-3997, may be effective in the treatment of bulimia and vomiting and that further investigation is warranted.
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PMID:The clinical efficacy of a 5-HT1A agonist, SM-3997, in the treatment of bulimia. 197 Dec 65

This investigation evaluated the antagonist properties of (-)propranolol, (+)propranolol, metergoline and BMY 7378 on the known effect of 8-OH-DPAT (DPAT) to decrease motion sickness in cats. (-)Propranolol produced a greater decrease in the antiemetic effect of DPAT than did (+)propranolol. Although metergoline produced a decrease in the antiemetic effect of DPAT, the decrease could not be clearly attributed to interactions with 5-HT1A receptors because metergoline alone slightly enhanced motion sickness. Depletion of 5-HT with PCPA produced a weaker, nonsignificant enhancement of motion sickness, while mesulergine had no effect. As neither nonspecific 5-HT receptor blockade with metergoline nor depletion of 5-HT mimicked the antiemetic effect of DPAT, it was concluded that DPAT acts on postsynaptic 5-HT1A receptors to prevent emesis. BMY 7378 alone decreased the incidence of motion sickness. A dose just below this agonist range did not decrease the effects of DPAT.
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PMID:Effects of serotonin antagonists on motion sickness and its suppression by 8-OH-DPAT in cats. 215 Apr 42

Work on the pharmacological effects of high-dose metoclopramide led Beecham scientists to identify the role of 5-HT3 receptors in the emetic response to cytostatic drugs and X-irradiation in animals. Further studies have confirmed and extended knowledge of the novel 5-HT3 antagonist granisetron. Dose-dependent inhibition of the 5-HT-induced Bezold-Jarisch reflex in anaesthetized rats was shown by doses of 0.1-10 micrograms/kg i.v. granisetron. Radioligand binding studies in rat brain revealed a high affinity (Ki 0.26 nM) for 5-HT3 sites and much lower affinities (Ki 1000 - greater than 10,000 nM) for 5-HT1, 5-HT2, 5-HT1A, 5-HT1B/C, 5-HT1C, alpha 1, alpha 2, dopamine D2, benzodiazepine, picrotoxin, beta, histamine H1 or opioid mu, kappa or delta binding sites. Granisetron was effective prophylactically after oral or i.v. doses or by intervention after i.v. doses (0.005-0.5 mg/kg) against cisplatin, cyclophosphamide and doxorubicin or X-irradiation-induced emesis in the conscious ferret in the absence of any side effects. It was concluded therefore, that granisetron is a selective and potent anti-emetic worthy of clinical investigation.
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PMID:The role of specific 5-HT3 receptor antagonism in the control of cytostatic drug-induced emesis. 216 86

Buspirone, an agonist of the 5-HT1A subtype of serotonin receptors, has shown antiemetic activity in animal models. However, in cancer patients treated with cisplatin, ondansetron, given either i.v. (one 8-mg dose 30 min after cisplatin) or orally (one 16-mg dose at the end of cisplatin infusion) was superior (P < 0.001) to buspirone (60 mg p.o. at the end of cisplatin and 60 mg p.o., 30 min later), in all parameters of antiemetic efficacy. These results are in favour of 5-HT3 receptors, but against the participation of 5-HT1A receptors in acute emesis associated with cisplatin chemotherapy.
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PMID:Comparative efficacy of a single oral dose of ondansetron and of buspirone against cisplatin-induced emesis in cancer patients. 754 13

Serotonin (5-HT) is a central neurotransmitter and a neuromodulator. This amine is involved in many physiological functions and pathological disorders. Most of its effects are mediated by specific 5-HT receptors. In the first part of this paper, the present knowledge of 5-HT receptors is reviewed in terms of both pharmacology and molecular biology. In the second part, the functional properties of 5-HT receptors are analyzed and their involvement in pathophysiological processes is discussed. Most 5-HT receptors belong to the G-protein-coupled receptor family (5-HT1, 5-HT2 and 5-HT4 receptors), whereas one is a member of the ligand-gated ion-channel receptor family (5-HT3 receptor). 5-HT1 receptors are characterized by their high affinity for 5-HT and comprise several subclasses. Most are negatively coupled to adenylate cyclase but the 5-HT1C subtype is linked to phospholipase C activation and resembles the 5-HT2 receptor. By contrast, the newly identified 5-HT4 receptor is positively coupled to adenylate cyclase. Most 5-HT receptors have now been cloned, but their physiological roles are not completely understood. Better knowledge of 5-HT receptors has already led to the development of new drugs, such as buspirone, a 5-HT1A partial agonist devoid of benzodiazepine-like properties for the treatment of generalized anxiety. Anxiolytic properties have also been reported for 5-HT2 and 5-HT3 receptor antagonists. A new and potent anti-migrainous drug, sumatriptan, has recently been selected among compounds obtained by research on the 5-HT1D receptor. This key receptor controls the release of monoamines, amino acids and peptides, and new drugs are expected in the near future. The therapeutic potential of 5-HT3 antagonists is impressive, as these compounds have potent antiemetic, promnesic and antipsychotic properties in various animal models. Two such drugs have already been marketed for the prevention of radiation-induced emesis (ondansetron and granisetron) and are more potent than the antidopaminergic drugs. Many other data suggest that 5-HT receptors might be involved in other illnesses. Some drugs are in the development phase but identification of the relevant receptor is often difficult. Furthermore, the lak of specific ligands for some receptors clearly hinders functional correlations.
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PMID:[Central serotonin receptors. Principal fundamental and functional aspects. Therapeutic applications]. 780 Oct 37

Ditolyguanidine (DTG) induced a dose-dependent emetic response in pigeons, with 100% of the birds vomiting after 5.6 mg/kg. Retching and vomiting originally induced by DTG could be conditioned to the test situation. Both the unconditioned and conditioned emetic responses were dose-dependently blocked by 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) and LY228729, agonists at the 5-HT1A subtype of serotonin receptor, but not by the 5-HT3, antagonist tropisetron. Higher doses (0.25-0.5 mg/kg) of tropisetron exhibited intrinsic emetic activity which could also be prevented by 8-OH-DPAT. NAN-190, a putative 5-HT1A partial agonist, produced both an antiemetic response when administered before DTG and also attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbital blocked the conditioned, but not the unconditioned DTG-induced emesis. These results support the possibility that 5-HT1A agonists exhibit antiemetic activity against a broad range of emetic stimuli, including conditioned vomiting which is usually resistant to pharmacological attenuation.
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PMID:Antiemetic effects of 5-HT1A agonists in the pigeon. 782 54

The antiemetic effects of flesinoxan were evaluated following s.c. administration in cats. Flesinoxan produced a dose-dependent suppression of motion sickness and also reduced xylazine-induced emesis at higher doses. Flesinoxan had a short latency to onset and may have a brief duration of action. It was slightly more potent that 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in contrast to their relative potencies on most other in vivo measures. High doses of both agonists produced defensive behavior as a result of 5-HT1A receptor stimulation. (-)-Propranolol, which previously reduced 8-OH-DPAT suppression of feline motion sickness, failed to reduce the antiemetic effect of flesinoxan. The dose of 3 mg/kg of NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine) produced a slight decrease in motion sickness and added to the suppression of motion sickness by low doses of flesinoxan via an uncertain mechanism. It also reduced the antiemetic effect of higher doses of flesinoxan. In contrast, NAN-190 produced additive antiemetic effects when combined with 8-OH-DPAT and little if any reduction. NAN-190 reduced the defensiveness produced by both flesinoxan and 8-OH-DPAT. Phentolamine and sulpiride reduced neither the antiemetic effect nor the defensive behavior produced by flesinoxan, thus ruling out a role for alpha-adrenoceptors and dopamine D2 receptors. Flesinoxan exerted a broad spectrum antiemetic effect by an action at 5-HT1A receptors as does 8-OH-DPAT, but differed in its response to putative 5-HT1A receptor antagonists.
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PMID:Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin. 801 49

The antiemetic effects of six serotonergic 5-HT1A-receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetrarin (8-OH-DPAT), 4-(4-[4-(2-pyrimidinyl)piperazin-1-yl]butyl)-2,3,4,5- tetrahydro-1,4-benzoxazepine-3,5-dione (SUN8399), buspirone, gepirone, ipsapirone and tandospirone, against motion sickness were investigated in Suncus murinus. Subcutaneous injection of all six agonists completely and dose-dependently suppressed motion-induced emesis. Pretreatment with 8-OH-DPAT or SUN8399 dose-dependently inhibited emesis elicited by nicotine (4.0 mg/kg, s.c.), veratrine (0.7 mg/kg, s.c.), cisplatin (20 mg/kg, i.p.) and copper sulfate (40 mg/kg, p.o.). These results suggest that serotonergic 5-HT1A-receptor agonists are effective as anti-motion sickness drugs, and these drugs may block a common mechanism(s) for the emetic reflex of the suncus because the antiemetic effects of the 5-HT1A-receptor agonists were exerted irrespective of the stimulus.
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PMID:Antiemetic effects of serotonergic 5-HT1A-receptor agonists in Suncus murinus. 802 27

Vomiting may be induced by a variety of agents such as drugs, oncolytics, and provocative motion, as well as being conditioned to occur to environmental stimuli. Such emesis has recently been shown to be blocked by agonists at the 5-HT1A subtype of serotonin receptor. The antiemetic effects of LY228729 [(-)-4-(dipropylamine)-1,3,4,5-tetrahydrobenz-(c,d)indole-6- carboxamide], a 5-HT1A receptor agonist, were tested and compared to the antiemetic effects of the 5-HT3 receptor antagonists ondansetron, tropisetron, and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate). The emetic stimuli tested are known to be blocked by 5-HT3 antagonists in species other than the pigeon. In the pigeon, LY228729 totally abolished vomiting induced by fully emetic doses of cisplatin (10 mg/kg), ipecac (3 ml/kg), emetine (10 mg/kg), and a 5-HT3 agonist, m-(chlorophenyl)-biguanide (1.25 mg/kg). MDL 72222 blocked ipecac-induced vomiting in a dose-related manner and was partially effective in attenuating cisplatin-induced emesis. Ondansetron and tropisetron were partially effective in blocking emetine- and mCPBG-induced vomiting. Ondansetron exhibited an intrinsic emetic response that could not be blocked by MDL 7222, but which was eliminated by LY228729. It was concluded that 5-HT1A agonists are more effective in the pigeon than are 5-HT3 antagonists against these types of emetic stimuli. These results broaden the range of emetic stimuli that are blocked by 5-HT1A agonists in the pigeon.
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PMID:Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon. 854 76

In the latter part of the 20th century, significant advances have been made in the understanding of the emetic reflex. As a result, there have been major improvements in the treatment of vomiting, particularly that associated with chemo- and radiotherapeutic treatments for neoplastic disease. The 5-HT3 receptor antagonists (ondansetron and granisetron) have been demonstrated to be of benefit in treating the profound emesis observed during cancer treatment. This observation, together with results from pharmacologic and physiologic investigations in both animals and humans, have identified 5-hydroxy-tryptamine (5-HT or serotonin) to be of fundamental importance in the pathogenesis of emesis. 5-HT appears to be released by radiation and chemotherapeutic agents from enterochromaffin cells within the wall of the intestine, and possibly from neurons within the brainstem. Stimulation of 5-HT3 receptors, located centrally in the dorsal medulla of the brainstem and peripherally on vagal afferent terminals in the gastrointestinal tract, appears to play a pivotal role in eliciting emesis. The interaction of 5-HT with non-5-HT3 receptors, particularly 5-HT1A and 5-HT4 receptors, may be important in the emetic reflex. The development of agents that interact with these receptors may offer alternative approaches to the treatment of nausea and vomiting.
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PMID:Serotonergic mediation of vomiting. 870 63


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