Dopamine releasing effect of phenylbiguanide in rat striatal slices

Abstract

The present study explored the mechanisms underlying the dopamine releasing effect of phenylbiguanide, a compound commonly used as a 5-HT3 receptor agonist. Phenylbiguanide, and also serotonin and 2-methyl-serotonin, enhanced the outflow of radioactivity from superfused rat striatal slices preloaded with [3H]dopamine. The presence of the dopamine uptake blocker nomifensin prevented the increase in outflow. The effect of phenylbiguanide was not antagonized by 5-HT3 receptor antagonists, did not require the presence of Ca2+ in the superfusion buffer, and also occurred in reserpinized preparations with depleted dopamine stores. Phenylbiguanide caused a greater shift in the distribution of superfusate radioactivity from DOPAC to dopamine than did nomifensin. All these results are in agreement with an exchange mechanism by which phenylbiguanide promotes the efflux of dopamine by operation of the uptake carrier in the reversed direction. In consonance, phenylbiguanide, and also serotonin and 2-methyl-serotonin, inhibited the binding of [3H]CFT to dopamine uptake sites, although the rank order for promoting outflow, serotonin greater than phenylbiguanide greater than 2-methyl-serotonin, differed from that for inhibiting [3H]CFT binding to dopamine uptake sites, 2-methylserotonin approximately serotonin greater than phenylbiguanide. The present results raised the possibility that phenylbiguanide has an additional activity in releasing vesicular dopamine into the cytoplasmic pool.

The Pharmacology of the Neurochemical Transmission in the Midbrain Raphe Nuclei of the Rat

“…The 5-HT 3 [22,145]. The latter effect was explained by reversemode operation of dopamine transporter.…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…These studies thus provide evidence that this effect is not 5-HT3 receptormediated. Instead, it can be blocked by a DA uptake inhibitor and thus appears to be carriermediated (Schmidt and Black, 1989;Benuck and Reith et al, 1992;Zazpe et al, 1994). An in vivo study also suggests that the 5-HT3 agonist phenylbiguanide can act at DA transporters to induce DA release.…”

Phenylbiguanide as electron donor in heterocyclic synthesis

“…Numerous reports have appeared in the literature, describing the cardiovascular reflexes [1][2][3][4][5][6], agonists and antagonists [3][4][5][6][7][8][9], visceral reflexes [10,11], and physiological [12] activity, as well as industrial [13][14][15][16][17] applications of arylbiguanides. Our long-term interest in chemical reactions induced by charge-transfer complexation forms a part of our systematic efforts to obtain new heterocyclic systems [18][19][20][21][22][23][24][25][26][27].…”