Influence of urapidil and 8-OH-DPAT on brain 5-HT turnover and blood pressure in rats.
The effects of urapidil, of the selective 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and of the alpha 2-adrenoceptor agonist clonidine on the in vivo rate of synthesis of 5-hydroxytryptamine (5-HT) were determined in rat brain cortex and hypothalamus. Urapidil (10 mg/kg), 8-OH-DPAT (0.3 mg/kg) or clonidine (0.3 mg/kg; all drugs i.p.) caused significant reductions in 5-HT synthesis rate. Pretreatment with the selective 5-HT1A receptor antagonist spiroxatrine (SPX; 1 mg/kg s.c.) or the nonselective 5-HT1 receptor antagonist metitepine (1 mg/kg i.p.) abolished the effects of urapidil and 8-OH-DPAT, but not of clonidine. The effects of urapidil and 8-OH-DPAT on mean arterial blood pressure (MAP) and heart rate (HR) of pentobarbital-anesthetized, normotensive rats were measured following stereotaxic microinjection into the B1/B3 cell region of the ventral medulla. The mean percentage decreases induced by urapidil (3 micrograms) and 8-OH-DPAT (0.2 micrograms) amounted to (MAP/HR) -13%/-6% and -19%/-25%, respectively. The following pretreatments markedly attenuated or prevented the effects of intramedullary injections of urapidil or 8-OH-DPAT: (a) SPX (1 mg/kg s.c., 60 min): (b) intracisternal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 0.2 mg; 7-10 days); (c) bilateral injection of 5,7-DHT at the cervical level of the spinal cord (each side 5 micrograms; 7-10 days). The present results are compatible with an action of urapidil as agonist at central 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Valenta
B
B
Institute of Pharmacology, University of Vienna, Austria.
Kotai
E
E
Weisz
E
E
Singer
E A
EA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013238:Stereotaxic Techniques; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D010879:Piperazines; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015568:urapidil; D003000:Clonidine