In vivo and in vitro pharmacological studies of a new hypotensive compound (QF0301B) in rat: comparison with prazosin, a known α1-adrenoceptor antagonist
2003; Elsevier BV; Volume: 40; Issue: 2 Linguagem: Inglês
10.1016/s1537-1891(02)00337-3
ISSN1879-3649
AutoresFrancisco Orallo, T. Garcia-Ferreiro, M. J. Enguix, Helena Tristán, Cristian F. Masaguer, Enrique Raviña, I. Cadavid, Marı́a Isabel Loza,
Tópico(s)Neuroscience and Neuropharmacology Research
ResumoIn this work, we studied the in vivo and in vitro pharmacological effects of the novel compound QF0301B (2-[2-(N-4-o-methoxyphenyl-N-1-piperazinyl)ethyl]-1-tetralone) and compared with those of prazosin. In anaesthetized normotensive rats, both QF0301B and prazosin (0.1–0.2 mg/kg iv) caused a pronounced and prolonged fall in mean arterial blood pressure accompanied by bradycardia. Neither QF0301B nor prazosin (0.2 mg/kg iv) significantly modified the cardiovascular effects of either 5-hydroxytryptamine (serotonin, 5-HT, 75 μg/kg iv) or the selective α2-adrenoceptor agonist B-HT 920 (0.2 mg/kg iv), but both markedly inhibited the hypertensive effect of noradrenaline (5 μg/kg iv), a nonselective α-adrenergic receptor agonist. In isolated rubbed rat aorta rings, QF0301B and prazosin showed marked α1-adrenoceptor blocking activity, with pA2 values of 9.00±0.12 and 9.75±0.14, respectively. In addition, QF0301B reversed and competitively antagonized the inhibitory action produced by clonidine in electrically stimulated rat vas deferens and inhibited the force and rate of contraction in rat isolated atria (pA2=5.91±0.43), competitively antagonized the contractile effect of 5-HT in rat aorta (pA2=6.75±0.06) and in rat stomach fundus (pA2=7.13±0.48) and the contractions induced by histamine in isolated guinea pig longitudinal ileal muscle (pA2=7.40±0.40). QF0301B showed noncompetitive low action in 5-HT3, muscarinic and nicotinic receptors, or as Ca2+ antagonist. These results indicate that a α1-adrenoceptor blocking lead has been obtained with a new chemical structure and interesting pharmacological properties, which only α1-adrenoceptor blocking activity seems to be responsible for its cardiovascular effects.
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