5-HT receptors mediating contractions of the isolated human coronary artery
ABSTRACT We investigated contractile responses of the isolated human coronary artery to 5-hydroxytryptamine (5-HT), washed human platelets, sumatriptan and ergotamine. 5-HT (pD2: 6.8 ± 0.1, Emax: 47.7 ± 6.8 mN) and platelets (effect 14.4 ± 2.8 mN with 3 · 1010 platelets/1) caused contractile responses which were attenuated by ketanserin (1 μM). In the presence of ketanserin (1 μM), both rauwolscine (1 and 10 μM) and cyanopindolol (1 and 10 μM) caused concentration-dependent additional antagonism against contractions induced by low (⩽ 1 μM) concentrations of 5-HT. Sumatriptan-induced contractions (pD2: 6.2 ± 0.1; Emax: 10.7 ± 2.4 mN) were antagonized to a similar extent by both rauwolscine (1 μM) and cyanopindolol (1 μM) (pKB: 6.5 ± 0.1 and 6.4 ± 0.1, respectively) and also by metergoline (0.1 μM; pKB: 7.2 ± 0.1). The order of potency of antagonists against sumatriptan resembles the order reported for the human saphenous vein 5-HT1D-like receptor. No significant additional antagonism by cyanopindolol (1 μM) or rauwolscine (1 μM) against platelet-induced contractile responses was observed. Ergotamine caused potent contractile responses (pD2: 8.4 ± 0.3, Emax: 19.4 ± 2.4 mN). It is concluded that although 5-HT2 receptors predominantly mediate 5-HT-induced contractions, the 5-HT1-like receptor seems to play a role in coronary vasospasm caused by low concentrations of 5-HT.
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ABSTRACT: Ischemic colitis (IC) is being increasingly recognized, although specific etiological causes are observed in a minority of patients. While several drugs have been associated with IC, most remain anecdotal reports. We recently treated a patient with IC thought to be related to sumatriptan for migraines, and performed a literature review along with a review of the FDA Adverse Event Reporting System (FAERS) database to identify additional cases. A MEDLINE/PubMed literature review was conducted using standard IC search terms to identify published cases of sumatriptan and other related "triptan" drug causes of IC. In addition, through a Freedom of Information Act request, we reviewed the adverse gastrointestinal events linked to sumatriptan contained in the FAERS database for the 5-year period 12 March 2008-11 March 2013, in order to determine whether unpublished cases might exist. Our case of IC was analyzed using a causality assessment tool initially developed for use in cases of alosetron (a 5-HT3 receptor antagonist)-related IC. Five published reports (containing a total of seven patients) describing sumatriptan-associated IC in the English language literature were found and reviewed. Another four published reports of related 5-HT1 receptor agonists causing IC (razitriptan n = 1 and naratriptan n = 3) were also analyzed. Among spontaneous reports of possible IC contained in the FAERS database for sumatriptan, there were 19 adverse events coded as "ischemic colitis" and another six coded as "intestinal ischemia" over a 5-year period ending March 2013, but clinical details were lacking. Similarly, five reports of possible IC from FAERS were mentioned in an earlier published report from the late 1990s. All of the published case reports of sumatriptan and related drugs were deemed to have the classic clinical findings and all recovered. There was one instance of possible recurrent IC symptoms in one patient re-exposed to sumatriptan, but not in another. We found that the IC scoring system developed for alosetron was applicable in our sumatriptan case. Among drug-related causes of IC, sumatriptan joins a growing list of agents with literature reports supported by the finding of suspected cases of IC in the FAERS database. However, the true incidence of IC due to sumatriptan, as well as other causes, cannot be accurately determined because of the likelihood of under-reporting. The structured IC scoring system appears to be applicable for drug-related as well as other etiological causes of IC.Drug Safety 01/2014; · 2.62 Impact Factor
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ABSTRACT: Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal discomfort, pain and changes in bowel habits, often associated with psychological/psychiatric disorders. It has been suggested that the development of IBS may be related to the body's response to stress, which is one of the main factors that can modulate motility and visceral perception through the interaction between brain and gut (brain-gut axis). The present review will examine and discuss the role of serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes in the pathophysiology and therapy of IBS. Search of the literature published in English using the PubMed database. Several lines of evidence indicate that 5-HT and its receptor subtypes are likely to have a central role in the pathophysiology of IBS. 5-HT released from enterochromaffin cells regulates sensory, motor and secretory functions of the digestive system through the interaction with different receptor subtypes. It has been suggested that pain signals originate in intrinsic primary afferent neurons and are transmitted by extrinsic primary afferent neurons. Moreover, IBS is associated with abnormal activation of central stress circuits, which results in altered perception during visceral stimulation. Altered 5-HT signaling in the central nervous system and in the gut contributes to hypersensitivity in IBS. The therapeutic effects of 5-HT agonists/antagonists in IBS are likely to be due also to the ability to modulate visceral nociception in the central stress circuits. Further studies are needed in order to develop an optimal treatment.Techniques in Coloproctology 01/2014; 18(7). · 1.54 Impact Factor
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ABSTRACT: The serotonin (5-hydroxytryptamine; 5-HT) 5-HT1-receptor agonist sumatriptan is a relatively new antimigraine drug. Some clinical trials and postmarketing surveillance studies of sumatriptan have demonstrated the occurrence of angina pectoris, cardiac arrhythmias and myocardial infarction that can be attributed to the use of the drug. At present the mechanisms of these adverse effects have not be determined. However, a possible relationship between migraine per se and cardiovascular disease, and an association between serotonin and cardiovascular disease, do exist. There are data to suggest that sumatriptan causes constriction of coronary arteries. In contrast, some investigators believe that the chest pains experienced by some patients who take sumatriptan are not of cardiac origin, but are due to oesophageal contractions. Whatever the cause, it can be concluded that, although severe cardiovascular adverse reactions to sumatriptan may be rare, every case of chest pain after administration of sumatriptan requires careful evaluation.CNS Drugs 02/1995; 3(2). · 4.38 Impact Factor