Influence of amineptine on changes of blood pressure evoked by norepinephrine and dopamine

Abstract

The influence of amineptine, an antidepressant currently employed having mainly selective dopaminergic neurochemical activity, on the pressor responses evoked by norepinephrine (NE) and dopamine (DA) was studied in anesthetized whole rats. Amineptine at doses of 0.5, 1.5, and 5.0 mg/kg/30 min infused into the femoral vein of the rat caused a dose-related inhibition of the pressor responses of NE and DA. The hypertensive responses of NE and DA augmented by pretreatment with reserpine, a catecholamine depletor, were also clearly depressed following the infusion of amineptine with a rate of 1.5 mg/kg/30 min. Furthermore, the pressor responses of NE and DA potentiated by pretreatment with debrisoquin, a sympathetic neuron blocker, were markedly diminished after pretreatment with the infusion of amineptine at the above same rate (1.5 mg/kg/30 min). These experimental results demonstrate that amineptine causes an inhibitory effect on the pressor responses evoked by NE and DA. It is thought that the amineptine effect may be due to the blockade of the peripheral adrenergic alpha-receptors in addition to the previously described uptake inhibition of dopamine.

Fig. 1

The chemical structure of amineptine

Fig. 2

Influence of amineptine (0.5 mg/kg. I.V.) on norepinephrine-evoked pressor responses. Amineptine was infused into a femoral vein at a rate of 0.5 mg/kg/30 min after obtaining control values of the norepinephrine-evoked pressor effects. The solid line denotes control responses before the administration of amineptine and the dotted line responses after amineptine. Abscissa: Pressor response evoked by norepinephrine in mmHg. Ordinate: Doses of norepinephrine in ug/kg. The vertical bars indicate standard error of the mean as compared with differences between the values before and after amineptine. The numeral in the upper bracket represents the number of experimental animals. ^*: pä0.05, NE: Norepinephrine

Fig. 3

Influence of amineptine (0.5mg/kg. I.V. on dopamine-induced pressor responses. Other legends and methods are the same as in Fig. 2. DA: dopamine, ^*: pä0.05

Fig. 4

Influence of amineptine (1.5 mg/kg. I.V.) on norepinephrine-evoked pressor responses. Other legends and methods are the same as in Fig. 2. ^**:pä0.01, ^***: pä0.001

Fig. 5

Influence of amineptine (1.5 mg/kg. I.V.) on dopamine-induced pressor responses. Other legends and methods are the same as in Fig. 2. ^*: pä0.05, ^**: pä0.01

Fig. 6

Influence of amineptine on norepinephrine-evoked pressor responses. Other legends and methods are the same as in Fig. 2. ^***: pä0.001

Fig. 7

Influence of amineptine (5.0 mg/kg, I.V.) on dopamine-induced pressor responses. Other legends and methods are the same as in Fig. 2. ^**: pä0.01, ^***: pä0.001

Fig. 8

The inhibition of norepinephrine-evoked pressor responses by amineptine. At arrow marks, the indicated doses of norepinephrine (0.15, 0.50, and 1.50 ug/kg) were given intravenously at 15-minute intervals. Between (A) and (B) amineptine (1.5 mg/kg/30 min) was infused into a femoral vein. Ordinate, blood pressor responses in mmHg. Time: 1 min. The black circle represents stoppage for 15 min.

Fig. 9

The inhibition of dopamine-evoked pressor responses by amineptine. Other methods and legends are the same as in Fig. 8.

Fig. 10

Influence of amineptine on pressor responses of norepinephrine potentiated by reserpine. Reserpine (3 mg/kg) was given intra muscularly about 48 hours before administration of amineptine. The solid line represents the response of norepinephrine 48 hours after reserpinization and the dotted line responses after amineptine (1.5 mg/kg/30 min, I.V.). Other legends and methods are the same as in Fig 2. ^**: pä0.01

Fig. 11

Influence of amineptine on pressor responses of norepinephrine potentiated by reserpine. Other legends and methods are the same as in Fig. 2 and 8. ^*: pä0.05, **:pä0.01

Fig. 12

Influence of amineptine on pressor responses of norepinephrine potentiated by debrisoquine. Debrisoquine was injected intravenously about 60 min before administration of amineptine. Other legends and methods are the same as in Fig. 2. and 10. ^**: pä0.01

Fig. 13

Influence of amineptine on pressor responses of dopamine potentiated by debrisoquine. Other legends and methods are the same as in Fig. 2. and 10. ^*: pä0.05, ^**: pä0.01