ISSN:0014-3022    

DOI:10.1159/000118886

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Efficacy with currently marketed antimigraine compounds is less than optimal. 311C90 is a novel and selective 5-HT1D receptor agonist in development for the acute treatment of migraine. It shows evidence of both central and peripheral activity within the trigemino-vascular system and it is rapidly absorbed following oral administration. In clinical studies in migraine patients, a headache response at 2 hours has been observed in 65–81% of patients at doses above 1 mg. Favourable response rates are reported as early as 1 hour post-dose and efficacy rates continue to improve up to 4 hours. Headache recurrence is reported by 25-35% of patients and 311C90 is also effective in relieving the non-headache symptoms of migrain

ISSN:0014-3022    

DOI:10.1159/000119096

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The tolerability of 311C90, a novel, selective and highly effective 5-HT1D receptor agonist in development for the acute treatment of migraine, has been evaluated in a number of clinical pharmacology and patient studies across the dose range 1-50 mg. 311C90 has been well tolerated across the entire dose range and no clinically relevant changes in routine laboratory parameters, blood pressure or ECG recordings have been observed. Adverse experiences reported are generally dose related, mild to moderate and resolve spontaneously. Chest-related symptoms occur infrequently and the cardiovascular safety profile of 311C90 is considered particularly favourable. 311C90, therefore, possesses a desirable safety profile which is well suited to broad-based outpatient adminstration.

ISSN:0014-3022    

DOI:10.1159/000119097

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Inappropriate activation of the trigemino-vascular system is thought to be important in the pathogenesis of a migraine attack. The 5-HTID agonist sumatriptan, which is highly effective in the acute treatment of migraine, inhibits trigemino-vascular activation in animals, although its actions are normally limited to peripheral components of the trigemino-vascular system. 311C90, a novel 5-HTID agonist drug, which is also highly effective in the acute treatment of migraine, acts not only at these sites, but, additionally within the brainstem, inhibiting trigemino-vascular activation centrally as well as peripherally. This article describes the pre-clinical development of 311C90 and considers, specifically, the approaches taken in the design of a molecule with attributes which facilitate access to brainstem components of the trigeminal pathway and combine this with good oral bioavailability.

ISSN:0014-3022    

DOI:10.1159/000119098

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000119099

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

311C90 is an orally active 5-HTID agonist with both central and peripheral actions that is currently being developed as an acute antimigraine treatment. Several studies have demonstrated the safety and efficacy of 311C90 in the treatment of a single migraine headache.The objectives of this open study are to assess the safety and efficacy of 311C90 when used for a period of up to one year. Patients can treat as many migraine headaches as desired with an oral treatment regimen of 311C90. An initial 5 mg dose for treatment of the migraine headache may be followed with a second 5 mg dose to treat recurrence should it develop. Safety assessments include electrocardiograms, the frequency, intensity and duration of adverse experiences, and routine haematology, urinalysis and clinical chemistry measures.Data presented here are an interim view of the database as of August 1995 and should be considered as preliminary observations. No clinically significant serious adverse experiences have been reported. The adverse experience and efficacy profile appears to be consistent with previous 311C90 studies and this dosing regimen of 311C90 was well tolerated during multiple exposures. Notably, response rates are as good after both initial and repeated exposure (up to 5 migraines).

ISSN:0014-3022    

DOI:10.1159/000119100

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The purpose of this pilot study was to determine whether 20 mg oral 311C90 can prevent the development of migraine headache when taken during the aura phase of a migraine attack. The study also aimed to provide an initial safety profile for 311C90 when taken during the aura. Forty patients (31 females, 9 males) were entered into this outpatient, double-blind, placebo-controlled, 2-period crossover trial. They all almost invariably experienced a migraine headache after the aura phase. Patients treated two migraine attacks during the aura phase in a random order, one with 311C90 20 mg and the other with placebo. Efficacy assessments were recorded on standard diary cards completed by each patient. A primary response was defined as the complete absence of headache pain in the 24 hour period following administration of the first dose of study medication. Safety assessments included ECGs, laboratory tests and the recording of adverse experiences. Twenty patients completed the study by treating 2 attacks, 16 of these were fully adherent to the study protocol. Three of the 16 patients responded to 311C90 whereas all patients developed a migraine headache after taking placebo. Two patients who did not respond to 311C90 described the developing headache as being ‘non-migraine’. Adverse experiences reported were similar to those experienced by patients in previous studies when 311C90 was taken during a migraine headache. There were no reports of 31 lC90-related adverse effects on the aura. These preliminary results suggest that oral 311C90 may be of value in preventing a migraine headache and is safe when taken during the aura phase. This intriguing possibility therefore warrants further investigation possibly utilising formulations that would deliver meaningful plasma levels of drug more rapi

ISSN:0014-3022    

DOI:10.1159/000119101

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000119102

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000119034

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000117208

出版商:S. Karger AG    

年代:1996

数据来源: Karger