Effects of urapidil on catecholamine turnover and release in the central nervous system of the rat

The actions of urapidil, prazosin, idazoxan, and haloperidol on the turnover of noradrenaline in the hypothalamus and dopamine in the nucleus accumbens of the rat were investigated using changes in the ratios of 3-methoxy-4-hydroxyphenyl-glycol/noradrenaline (MHPG/NA) and 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA), respectively, as measures for drug-induced effects. Urapidil (2.5-30 mg kg-1 i.v.) increased the ratios of MHPG/NA and DOPAC/DA. Its effects on NA turnover were maximal at 60 min (160% of control at 30 mg kg-1), and on DA turnover at 30 min (138% of control at 30 mg kg-1). Prazosin (0.5-2.5 mg kg-1 i.v.) had no effect, but the high dose of 5 mg kg-1 i.v. significantly increased the ratio of MHPG/NA in the hypothalamus. Idazoxan (2-50 mg kg-1 i.v.) and haloperidol (0.02-0.5 mg kg-1 i.v.) selectively enhanced turnover of NA and DA, respectively. In experiments on field-stimulated overflow of tritium from slices of hypothalamus and nucleus accumbens labelled with [3H]NA or [3H]DA, respectively, urapidil (1 mumol L-1) facilitated the evoked responses in both regions. Prazosin (0.1 mumol L-1) had no effect in either of the two areas. Idazoxan (0.1 mumol L-1) increased stimulated overflow of [3H]NA from the hypothalamus but not of [3H]DA from the nucleus accumbens. Conversely, haloperidol (0.1 mumol L-1) greatly enhanced evoked overflow of [3H]DA but not of [3H]NA. From the present results it is concluded that urapidil has an antagonistic effect at central alpha 2-adrenoceptors and also a weak antagonistic action at central dopamine D2-receptors.