Differentiation of the neurobiological effects of amphetamine and amphetamine like stimulants

Objectives To compare the central dopamine-releasing effects of (+)amphetamine and (+)phentermine.

Methods Positron emission tomography (PET) was performed twice for 90 min following the IV injection of 740 MBq (20mCi) [11C]raclopride on 40 healthy normal control participants. (A) Four participants (2 men and 2 women) aged 22 to 29 received a single-blind oral administrations of (a) placebo 5 min before the 1st PET scan and (b) 30 mg (+)-phentermine 90 min before the 2nd PET scan . (B) Thirty-six different participants (22 men and 14 women) aged 18 - 29 received single-blind IV administrations of (a) saline before the 1st PET scan and (b) 0.3 mg/kg (+)-amphetamine 5 min before the 2nd PET scan. Plasma levels of norepinephrine(NE) and prolactin was obtained during both studies. The dopamine release (DAR) was calculated using the [11C]raclopride displacement method.

Results Intrasynaptic DAR was significantly increased following the administration of (+)amphetamine, but not with (+)phentermine (See Table). After the (+)phentermine there was a negligible decrease in mean plasma level of prolactin and an increasing trend in mean plasma level of NE.

Conclusions Both (+)amphetamine and (+)phentermine produce classic psychostimulant effects in humans (George, et al., NRM12_All_Abstracts.pdf, 2012, nrm12.org).This study indicated no changes in DAR after (+)phentermine. In light of the well-documented NE releasing effect of (+)phentermine at these oral doses. The results suggest that NE release contributes to psychostimulant effects in humans.These findings may facilitate the development of effective novel treatments for stimulant abuse and dependence.

Research Support PHS Grants MH078175, NS38927, DA00412, AA12839, GCRC (NIH/NCRR M01RR00052), The Brain and Behavior Research Foundation (NARSAD), The Essel Foundation, and the Tourette Syndrome Association