Oral sumatriptan administration has been reported to delay gastric emptying after liquid meals. The aim of this study was to determine whether delayed gastric emptying is caused by enhanced gastric accommodation, impaired antral contractions, or both using ultrasonography.

Ten healthy volunteers were enrolled in this randomized two-way crossover study. After overnight fasting, the subjects received the liquid meal 60 min after ingesting a 50 mg sumatriptan tablet with 50 mL of water or 50 mL of water alone (control). The cross-sectional area of the proximal stomach was measured in a supine position after every 100 mL. The frequency and amplitude of the antral contractions were measured in a slightly backward sitting position. The intragastric distribution of the liquid meal was assessed by calculating the proximal stomach/distal stomach ratio (prox/distal ratio).

The cross-sectional area after drinking 100, 200, and 300 mL of the liquid meal (oral sumatriptan vs control) was 34.49 vs 15.11 cm(2) (P = 0.0051), 48.00 vs 30.61 cm(2) (P = 0.0166), and 58.67 vs 47.19 cm(2) (P = 0.0125), respectively. There was no significant difference in the amplitude of contractions, contraction cycle, motility index, and prox/distal ratio (97.15 vs 97.93%, P = 0.0745; 19.42 vs 19.5 s, P= 0.8590; and 887.58 vs 889.22, P = 0.5751; 9.75 vs 8.41, P = 0.8785; respectively).

Oral sumatriptan administration enhanced gastric accommodation after the ingestion of liquid nutrients, but had no significant effect on antral contractions or intragastric distribution in healthy subjects.

The paradigm of early treatment of the migraine attack at mild pain intensity has become one alternative to circumventing the problem of compromised oral absorption of symptomatic drugs due to migraine-induced gastrointestinal dysmotility. Early treatment also has been proposed to be advantageous because most migraineurs could be less responsive to delayed treatment, owing to the development of central sensitization of the trigeminal pain transmission. Ranking the underlying principles, it seems that the improved response to an oral triptan formulation at mild migraine symptom intensity has more to do with less impaired gastrointestinal absorption in the early stage of the attack than decreasing the time and preventing chances for central sensitization and development of cutaneous allodynia. Furthermore, parenteral administration of a triptan is always more likely to provide relief of symptoms than conventional tablets, even when it is used later in the course of the migraine attack. Individually tailored use of the available triptan formulations will increase, without any doubt, the within-migraineur consistency of response. It also will reduce the overall proportion of migraine attacks or migraineurs not responding to triptan treatment. Notwithstanding, the recommendation of early treatment during the migraine attack when the pain is mild remains valid.

The aim of this study was to determine whether in migraine patients with and without aura early treatment with various triptans leads to differences in pain reduction after 1 h and in modulating cutaneous allodynia. Thirty-six patients with early manifestation of a clinically recognizable allodynia of the face and non-responders to earlier treatment with sumatriptan 100 mg were included. Patients were randomized to six triptan treatment groups. Significant pain reduction was seen only in the group receiving zolmitriptan nasal spray 5 mg with a mean visual analogue scale (VAS) score of 3.8 (s.d. 1.2) at baseline and 2.4 (s.d. 1.3; P = 0.015) at 1 h after using the triptan and was thus a predictor of a VAS score 3 within 1 h. The study results indicate that migraine headache intensity can be reduced within 1 h by using zolmitriptan 5 mg nasal spray in spite of the presence of early cutaneous allodynia.

The introduction of triptans (5-HT (1B/1D) agonists) into clinical practice has expanded the therapeutic options for doctors treating migraine sufferers. The triptans are available in several different formulations such as conventional oral tablets, orally disintegrating wafers, subcutaneous injections, nasal sprays, and suppositories, which provide an excellent opportunity to tailor therapy to individual patients' needs. Although the oral formulations are the most popular with patients, they are not the most appropriate route of administration for drug delivery during the migraine attack. Due to gastrointestinal dysmotility, the intestinal absorption of any triptan administered orally may be impaired and treatment effects become inconsistent. For this reason, triptans preferably should be prescribed in a non-oral formulation (injection, nasal spray, or suppository). Parenteral administration of a triptan is more likely to provide relief of symptoms, even when it is used later in the course of the migraine attack.

Migraine is a chronic, neurological disorder generally manifesting itself in attacks with severe headache, nausea and an increased reactivity to sensory stimuli. A low migraine threshold is set by genetic factors, although the phenotype also modulates the manifestations. The 1-year prevalence is approximately 13% and is higher among women. Patients usually experience neuropsychological dysfunction, and sometimes also reversible focal neurological symptoms. The trajectories of the characteristic symptoms of acute migraine usually follow a similar time course, indicating a reciprocal underlying mechanism. A central nervous system hyperexcitability has been demonstrated in neurophysiological studies. The dibilitating effects of migraine are not confined to the attacks per se. Many individuals do not recover completely between the attacks and most report a negative impact on the most important life domains, and an interest in testing other treatments. Young persons have a higher frequency of attacks. Acute treatment should routinely be initiated with an analgesic plus a prokinetic anti-emetic. Triptans must not be provided early during the attack to ensure their efficacy. The natural course of attacks is commonly only temporarily altered by acute treatment. Non-pharmacological treatment and drugs may be equally viable in prophylaxis for migraine. In more complicated cases, conjoint therapy should be considered. New strategies to improve adherence with existing therapeutic regimens might yield greater benefits than will new pharmacological agents.

Conventional taste-masking strategies are used to overcome the bitter taste perception of pharmaceuticals by coating the drug particles and/or adding flavoring agents. However, for certain product categories such as rapid dissolve sublingual tablets, taste-masking is challenging. Programs exploring such formulation strategies in the LO-CS phase or post CS phase possess very little toxicological information available in order to conduct human taste panel studies. The potential of a bitter taste perception can present a significant business risk. The objective of the study was to validate a rat behavioral avoidance model that identifies bitter-tasting compounds. Most classic bitter substances elicit a response in the micromolar concentration range while most drugs elicit a response in the millimolar range, hence a validation exercise was conducted to examine if the existing biological model was sensitive enough to identify known bitter tasting drugs as such. Five compounds: ergotamine tartrate, fluoxetine, sucrose, sumatriptan and povidone were chosen to represent a spectrum of compounds. The bitter tasting compounds were identified as such in the model. Based on these results, the assay may serve as a useful surrogate test to identify compounds that may have bitter taste issues.

In the past decade, several studies have reported a significant delay of gastric emptying induced by the anti-migraine agent sumatriptan (a 5-hydroxytryptamine (5-HT)1B/D receptor agonist) in healthy human beings. In patients with functional dyspepsia, sumatriptan improves gastric accommodation after food consumption and reduce perception of gastric distension, hence relieving epigastric symptoms. Recent studies have established that impaired accommodation after food consumption is a major patho-physiological mechanism in functional dyspepsia and restoration of accommodation is considered to be a potential therapeutic target. The precise site of action of sumatriptan in humans is at present unknown, although recent studies carried out using a canine model indicate that sumatriptan exerts its action on gastric accommodation through 5-HT1B receptors, since both GR127935 and SB216641 (respectively, non selective 5-HT1B/D and selective 5-HT1B receptor antagonists) fully antagonised the effects of sumatriptan. Gastric relaxation and enhanced accommodation to a distending stimulus seem to be a class effect of triptans, since it occurs not only with sumatriptan, but also with second-generation triptans (rizatriptan and naratriptan), at least in a canine model. In dyspeptic patients, administration of triptans would be able to restore gastric accommodation after a meal and to improve symptoms of early satiety, confirming the therapeutic potential of 5-HT1B/D receptor agonists in functional dyspepsia.

The triptans represent a relatively new class of compounds effective in the treatment of migraine. The safety and tolerability of these drugs have been extensively investigated since the first triptan (sumatriptan) became commercially available. A report on a very large population of patients tested during clinical trials and in postmarketing studies, confirms that these drugs are safe and well tolerated when correctly used. Adverse events are frequently reported, but are usually mild and only a few patients discontinue therapy because of them. These adverse events include, in particular, the so-called 'triptan symptoms' (tingling, sensation of warmth, etc.). The exact mechanism of chest symptoms reported by 20% of patients with migraine treated with triptans remains unclear, but are exceptionally related to a cardiac mechanism. CNS adverse events (i.e. somnolence) are also reported, but it is a matter of debate whether they are related to the pharmacological properties (i.e. lipophilicity) of the drug or are symptoms of the disease itself. The potential risk for drug overuse must be taken into account when the triptans are given to patients with a high frequency of migraine attacks. Clinical interaction of triptans with other drugs metabolised in the liver may theoretically influence the incidence of adverse events, but there is little evidence to support this assumption. There is no evidence of a teratogenic risk of triptans in pregnant women taking these drugs.

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria. The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia. Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT(4) receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT(4) receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT(3) receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK(1)/NK(2)) and cholecystokinin (CCK)(1) receptors.

The triptans (selective serotonin agonists) are becoming the first-line alternatives in the acute pharmacological treatment of migraine, at least for attacks of moderate-to-severe intensity. Although clinical trials demonstrate significant differences in efficacy between triptan tablets, they often appear similar in efficacy when used in clinical practice, particularly after dose adjustments. Most patients with migraine consider drugs that can be administered orally to be the most user-friendly. However, gastrointestinal absorption may be impaired during migraine attacks because gastric motility is inhibited, and there is a risk that nausea during the attack will culminate in vomiting. Furthermore, in addition to their antimigraine properties, triptans may prolong the gastric emptying time. For this reason the absorption of any triptan taken orally during the migraine attack will be erratic and treatment effects inconsistent. Despite these barriers to good efficacy and high reliability, the tablet is the most commonly used triptan formulation.