Antagonistic properties of RU 24969, a preferential 5-HT1 receptor agonist, at presynaptic alpha 2-adrenoceptors of central and peripheral neurones.
The effect of RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1 H-indole) on the electrically evoked 3H overflow was studied in superfused rat brain cortex slices preincubated with 3H-noradrenaline or 3H-serotonin and in superfused segments of the rat vena cava preincubated with 3H-noradrenaline. In cortex slices preincubated with 3H-noradrenaline, RU 24969 facilitated the electrically (3 Hz) evoked 3H overflow. This effect was abolished by phentolamine but was not affected by desipramine or the 5-HT3 receptor antagonist ICS 205-930. The concentration-response curve of noradrenaline for its inhibitory effect on the evoked overflow (determined in the presence of desipramine) was shifted to the right by RU 24969 32 and 100 mumol/l. In this respect, RU 24969 was about 500 times less potent than phentolamine. In cortex slices preincubated with 3H-serotonin, the inhibitory effect of 3.2 mumol/l RU 24969 on the electrically evoked 3H overflow was increased by phentolamine. In segments of the vena cava, RU 24969 inhibited the electrically (0.66 Hz) evoked 3H overflow. The concentration-response curve of RU 24969 was U-shaped, since at concentrations higher than 0.1 mumol/l the extent of inhibition decreased with increasing concentrations of RU 24969. In the presence of phentolamine, the concentration-dependent attenuation of the RU 24969-induced inhibition of overflow was no longer detectable. The present results suggest that RU 24969 is a weak antagonist at presynaptic alpha 2-adrenoceptors (by more than 2.5 log units less potent than as an agonist at presynaptic 5-HT1B auto- and heteroreceptors).
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D014684:Venae Cavae / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D011985:Receptors, Serotonin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D009638:Norepinephrine; D010646:Phentolamine