Effects of 5-HT_1B/1D Receptor Agonist Rizatriptan on Cerebral Blood Flow and Blood Volume in Normal Circulation

Abstract

To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT 1B/1D ) receptor agonists for migraine treatment, changes in cerebral blood flow (CBF) and blood volume induced by rizatriptan were assessed by positron emission tomography (PET). Eleven healthy volunteers underwent PET studies before and after rizatriptan administration. Dynamic PET data were acquired after bolus injection of H 2 15 O to analyze CBF and arterial-to-capillary blood volume (V 0 ) images using the threeweighted integral method. After a baseline scan, three further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug administration. Global and regional differences in CBF and V 0 between conditions were compared using absolute values in the whole brain and cortical regions, as well as statistical parametric mapping (SPM) analysis. The global and regional values for CBF and V 0 decreased significantly after rizatriptan administration compared with the baseline condition. However, both values recovered to baseline within 80 mins after treatment. The maximal reduction in global CBF and V 0 was approximately 13% of baseline value. The greatest decrease in CBF was observed approximately 60 mins after drug administration, whereas the maximal reduction in V 0 was observed approximately 5 mins earlier. Statistical parametric mapping did not highlight any regional differences between conditions. Thus, in brain circulation, rizatriptan caused significant CBF and V 0 decreases, which are consistent with the vasoconstrictor effect of triptans on the large cerebral arteries. The gradual recovery in the late phase from the maximal CBF and V 0 decrease suggests that rizatriptan does not affect the cerebral autoregulatory response in small arteries induced by CBF reduction.

Vasodilatory effect of adenosine triphosphate does not change cerebral blood flow: a PET study with 15O-water

“…The relaxation of vascular smooth muscles by the stimulation of the A2 receptors [7,23] did not change CBF in the cerebral cortices, which goes in line with previous reports studied with adenosine [24,25]. This no change in CBF despite vasodilation in the major vessels is considered to be caused by systemic hypotension due to vasodilation in peripheral arteries and the cerebral microvascular autoregulation which preserves intracranial perfusion pressure [22]. Vasodilatory change with decrease in systemic blood pressure usually causes reduction of blood flow; however, slight vasodilatory change in major cerebral arteries may induce constriction of arterioles and restore blood flow immediately by the well-known function of microvascular autoregulation [22].…”

“…This no change in CBF despite vasodilation in the major vessels is considered to be caused by systemic hypotension due to vasodilation in peripheral arteries and the cerebral microvascular autoregulation which preserves intracranial perfusion pressure [22]. Vasodilatory change with decrease in systemic blood pressure usually causes reduction of blood flow; however, slight vasodilatory change in major cerebral arteries may induce constriction of arterioles and restore blood flow immediately by the well-known function of microvascular autoregulation [22]. There was no change in CVR between different conditions which supports this assumption.…”

“…In the SPM analysis, each CBF image was smoothed using a Gaussian filter (12 mm FWHM) and the pixel values were normalized so that the global mean of CBF should be 50 mL/min/100 g. Analysis of covariance (ANCOVA) was used for evaluation of regional difference [20]. To identify the regions showing significant differences, the height threshold (u) and the extent threshold (k) were set at p = 0.001 and k = 100, respectively [22]. Table 1 shows the mean of CBF, blood pressure, heart rate and CVR in different conditions in all subjects.…”

A review of diagnostic and functional imaging in headache

“…Together, these imaging data strongly suggest that migraine aura is not evoked by ischaemia, but is more likely due to an electrophysiological event such as CSD [34]. Given that the global and regional values for cerebral blood flow decreased significantly after triptan administration, the aura data also underline that potentially vasoconstrictive agents, such as triptans or ergots, should not be used during the aura phase of migraine [36]. …”

The Comparıson Of Trıptans, Nsaıd Or Combınatıon On Mıgraıne Attack Treatment

“…[20] Sağlıklı katılımcılar üzerinde yapılan bir çalışmada rizatriptan belirgin şekilde beyin kan akımını azaltmış, arterden kapillere geçen kan hacmini geniş arterler üzerindeki vazokonstrüksü-yon etkisiyle azaltmış, küçük arterlerin otoregulatuvar sistemlerinde değişikliğe sebep olmamıştır. [24] Rizatriptan gastrointestinal yoldan hızla ve tama yakın (%90) emilir. Oral tablet 10 mg formunda en fazla plazma konsantrasyonuna ulaşması için geçen ortalama süre 1-1.5 saattir.…”