In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced 
lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have 
been approved for marketing in most countries of the world (naratriptan, 
rizatriptan and zolmitriptan). In addition, at least three others are in 
advanced stage of clinical development (almotriptan, eletriptan, and 
frovatriptan). This paper sets out to review the recent data with the aim of 
identifying: 1) What are the critical differences between the TELs and 
sumatriptan? 2) How do the currently licensed TELs compare? 3) Is it possible to 
provide a rational approach to migraine therapy based on objective differences 
in the clinical profile of these new drugs? Recent randomised controlled and 
comparator data were reviewed, including the independent FDA assessment of 
rizatriptan. Critical differences for the new TELs (naratriptan, rizatriptan and 
zolmitriptan) which may lead to more rational migraine management: Both 
rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5.0 mg) have demonstrated 
superior efficacy to sumatriptan 100 mg, and 25 and 50 mg respectively. 
Therefore, for first line use either rizatriptan or zolmitriptan would be 
appropriate for moderate and severe headache. Rizatriptan has a more rapid onset 
of action than sumatriptan 100 mg. Both rizatriptan and zolmitriptan have a more 
rapid onset of action than naratriptan. Therefore, for a rapid onset of action 
either rizatriptan or zolmitriptan would be appropriate. Naratriptan would 
appear to have a lower recurrent headache rate than sumatriptan, rizatriptan or 
zolmitriptan. However, 24-hour efficacy rates for zolmitriptan 2.5 mg were 
significantly greater than for sumatriptan 25 mg and 50 mg and were not 
significantly different from naratriptan. Therefore, for headaches of long 
duration and with a tendency to recur (e.g. menstrual headaches) either 
naratriptan or zolmitriptan would be appropriate. Naratriptan has lower reported 
adverse event rates comparable with placebo. This would support the use of 
naratriptan 2.5 mg in patients who have demonstrated poor tolerance to the 
"triptan type" adverse events.