Mazindol dopamine transporter

Fig. 3. These figures demonstrate that regenerated terminals a have dopamine transport with reduced velocity and affinity. However the D2R appears to be normally responsive to quinpirole suggesting that it has normal function, (a and b) Scatchard plots of [3H]Mazindol binding to the DAT in the dorsal striatum, (a) normal animals and (b) lesioned animals. Data from normal animals required a two-line fit indicative of two distinct binding sites, one of high affinity and a second of lower affinity. Following partial SNpc lesions, the scatchard plots also required a two-line fit. Although the Kd of high affinity sites in lesioned and unlesioned animals were similar, density was reduced by almost 40% in lesioned animals. In contrast, the low affinity site had a very high...

Fig. 15. Dopamine transporter binding (as revealed by [3H] mazindol in the presence of desmethylimipramine, to block binding to the norepinephrine transporter) in the post-mortem striatum of a human cocaine user and normal control subject. A reduction of the dopamine transporter binding sites was found in association with cocaine use in this population (taken from Hurd and Herkenham, 1993).

Some antidepressants, notably mazindol and bupropion (3), inhibit the dopamine transporter (DAT) as well as NET or SERT. The DAT is best known, however, as one of the principal sites of action of the psychostimulant drug cocaine. Mice that are genetically engineered to knock out the expression of the DAT gene are profoundly hyperactive and fail to show any further stimulation of activity in response to cocaine or (-i-)-amphetamine (109). Such animals, nevertheless, will continue to self-administer cocaine (110), suggesting that the rewarding properties of the... 

Kulkarni, S.K, Newman, A.H. and Houlihan, W.J. (2002) Three-dimensional quantitative structure-activity relationships of mazindol analogues at the dopamine transporter. /. Med. Chem., 45, 4119-4127. 

Mazindol (Sanorex ) is a phenyl-substituted imidazobenzoisoindole that inhibits both NE and dopamine reuptake transporters. It exhibits high affinity for the NET (rat pKj = 9.3), good affinity for dopamine transporter (rat pKj = 7.8), and a 5-HT NE ratio of 224. Dopamine reuptake inhibitors suppress appetite thus, mazindol is approved to be marketed as an appetite suppressant. 

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