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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of RX 821002 at 5-HT1A-receptors in rabbit spinal cord in vivo.

1. The activity of RX 821002 (2-methoxy idazoxan) at 5-HT1A-receptors in the spinal cord has been investigated in decerebrated, spinalized rabbits. Reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve were unaffected by intrathecal ( administration of RX 821002 (111 and 664 nmol cumulative, n = 7), although the highest dose of this drug did produce a significant increase in heart rate of 28 +/- 7 beats min(-1). Subsequent administration of the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) at 300 nmol,, facilitated reflexes to a median of 144% of pre-drug controls, an effect that was partially reversed (to a median value of 120% of pre-drug values) by subsequent administration of the 5-HT1A-receptor antagonist WAY-100635, at 185 nmol 2. In a separate set of experiments, 8-OH-DPAT was given at 30 nmol and potentiated reflexes to a median of 170% of pre-drug levels (n = 8). Subsequent administration of RX 821002 (at a cumulative dose of 1.11 micromol,, n = 5) significantly reduced gastrocnemius responses to a median of 154% of control values. 3. After a 3 h recovery period, 8-OH-DPAT was re-administered at 30 nmol,, and increased reflexes to a median value of 151% of pre-drug levels, an effect not significantly different from when it was given alone. WAY-100635 dose-dependently antagonized this effect, causing significant reductions in reflexes at a cumulative dose of 0.55 nmol,, and complete reversal of the effects of 8-OH-DPAT at a cumulative dose of 5.5 nmol. 4. These data show that, at intrathecal doses up to 664 nmol, RX 821002 is devoid of agonist activity at 5-HT1A-receptors. It appears to be a very weak antagonist at these sites in vivo, being some 2000 times less potent than WAY-100635. The inability of WAY-100635 to block completely the effects of high doses of 8-OH-DPAT has been noted previously and can be explained by non-selective actions of the agonist. However, it would appear that a 30 nmol dose of 8-OH-DPAT is selective for 5-HT1A receptors in this preparation.[1]


  1. Effect of RX 821002 at 5-HT1A-receptors in rabbit spinal cord in vivo. Ogilvie, J., Clarke, R.W. Br. J. Pharmacol. (1998) [Pubmed]
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