Skip to main content

Table 1 Studies on the central nervous system effect of sumatriptan in animals

From: Does sumatriptan cross the blood–brain barrier in animals and man?

References

Dose of sumatriptan

Parameter used

Results

Indicates passage of sumatriptan across BBB

Sleight et al. (1990) [11]

50 and 500 μg/kg (i.p.) (guinea pig)

Extracellular 5-HT levels in the frontal cortex as measured by microdialysis

No effect of systemic sumatriptan (sumatriptan 10−8–10−7 M in microlysate caused a decrease of 5-HT)

Skingle et al. (1990) [24]

Dose 1–100 mg/kg (rodents)

Antinociceptive effect by (various tests)

No antinociceptive effect (in some tests 100 mg/kg had an effect)

Nozaki et al. (1992) [36]

720 nmol/kg (300 μg/kg) (rat)

c-fos expression in the trigeminal nucleus caudalis after autologous blood in cisterna magna

Sumatriptan reduced c-fos positive cells in trigeminal nucleus caudalis by 31%

(−/+) see commenta

Moskowitz et al. (1993) [37]

300 μg/kg (rats

c-fos expression in trigeminal nucleus caudalis after repeated CSD

Sumatriptan reduced c-fos expression

(−/+) see commenta

Kaube et al. (1993) [12]

100 μg/kg (cat)

Single units activity and trigeminal somatosensory evoked potentials after SSS stimulation

No effect of sumatriptan (after blood–brain barrier disruption with mannitol sumatriptan decreased the peak-to-peak amplitude of evoked potentials)

Shepheard et al. (1995) [13]

1,000 μg/kg (rat)

Expression of c-fos mRNA in trigeminal nucleus caudalis after stimulation of trigeminal ganglion

No effect of sumatriptan (after blood–brain barrier disruption with mannitol sumatriptan decreased expression of c-fos mRNA with 63%

Ghehardini et al. 1996 [28]

5–30 mg/kg (mouse))

Antinociceptive effect (hot-plate test)

There was an antinociceptive effect, most likely mediated by the 5-HT1A receptor

?

Mitsikostas et al. (1996) [30]

0.3–0.9 mg/kg (rat)

Brain monoamines concentration

0.6 mg/kg decreased hypothalamic serotonin concentration

+

Hoskin and Goadsby (1996) [29]

85 μg/kg (cat)

c-fos expression in trigeminal nucleus caudalis after dilatation of SSS

Reduction of c-fos expression

(+/−) see commentsb

Knyihár-Csillik et al. (1997) [14]

120 μg/kg (rat)

c-fos in caudal trigeminal nucleus after stereo electrical stimulation of the trigeminal ganglion

No effect of sumatriptan on c-fos expression

Ingvardsen et al. (1997) [27]

300 μg/kg (rat)

c-fos in TNC after CSD

No effect of sumatriptan on c-fos expression

Hoskin and Goadsby (1998) [5]

85 μg/kg (rat)

c-fos expression in trigeminal nucleus caudalis after SSS stimulation

No effect on c-fos expressionb

Read et al. (1999) [31]

300 μg/kg (rat)

Nitric oxide formation in the cerebral cortex after nitroglycerin

Decrease of NO formation

+

Read and Parsons [32]

300 μg/kg (rat and cat)

Nitric oxide formation in the cerebral after CSD

Decrease of NO formation and decrease of partial oxygen tension

+

Read et al. (2001) [25]

300 μg/kg (rat)

CGMP after CSD

No effect on brain stem cGMP after 3 days

Johnson et al. (2001) [20]

3.2 mg/kg (rat)

Measurements of sumatriptan concentrations in microdialysate. Central release of 5-HT

Concentrations of sumatriptan up to 8 nM was observed. No effect on central release of 5-HT

+

Kayser et al. (2002) [33]

100 μg/kg (rat)

Mechanical allodynia-like behaviour after ligature of n. infraorbitalis

A significant reduction of mechanical allodynia-like behaviour on injured and contralateral side of the facec

+

Dobson et al. (2004) [34]

300–1,000 μg/kg (rat)

Serotonin synthesis in brain

Given acutely a decrease in 5-HT synthesis in certain regions of the brain was observed

+

Pardutz et al. (2004) [26]

600 μg/kg (rat)

Nitroglycerin-induced nNOS immunoreactive neurones in trigeminal nucleus caudalis

nNOS expression could not be prevented

Levy et al. (2004) [21]

300 μg/kg (rat)

Changes in spontaneous activity of trigeminal peripheral and central neurones after inflammatory soup on dura

Sumatriptan blocked the induction of central sensitization most likely by a presynaptic inhibition

+

Edelmayer et al. (2009) [22]

600 μg/kg (rat)

Prevention of facial allodynia after inflammatory mediators on the dura

Sumatriptan prevented or reversed facial allodynia

+

Bates et al. (2009) [35]

600 μg/kg i.p. and 0.06 μg intrathecal (mouse)

Prevention of thermal and mechanical allodynia

Systemic sumatriptan inhibited thermal allodynia but not mechanical allodynia. Intrathecal sumatriptan inhibited both

+

  1. aThe authors considered that this was a peripheral effect on the trigeminal nerve [34], see text
  2. bThe authors concluded: “The simplest reasonable conclusion is that sumatriptan inhibited trigeminal afferent by a direct neuronal mechanism at the peripheral terminal.”[22]. They found a central effect unlikely because no central effect of sumatriptan was observed in previous studies [9, 10]
  3. cZolmitriptan 30 μg/kg caused a decrease in c-fos expression in trigeminal nucleus caudalis
  4. dThe site of action is not totally clear but is most likely a CNS effect because a reduction of contralateral allodynia [29]