Synthesis and dopaminergic activity of (+-)-, (+)-, and (-)-2-dipropylamino-5-hydroxy-1,2,3,4-tetrahydronaphthalene

Abstract

In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.

Pharmacokinetics and Pharmacodynamics Analysis of Transdermal Iontophoresis of 5-OH-DPAT in Rats: In vitro–in vivo Correlation

“…Dopamine agonist ( R , S )‐5‐hydroxy‐2‐( N , N ,‐di‐ n ‐propylamino)tetralin (5‐OH‐DPAT) is one of the most potent compounds from 2‐aminotetralin group 3. However, due to extensive first pass metabolism resulting in a low oral bioavailability (approximately 1%4), its utility in Parkinson's disease therapy is limited.…”

Effect of 8-hydroxy-2-(di-n-propylamino) tetralin on rat prolactin secretion

“…Many aminotetralin derivatives have been characterized as having dopamine agonist properties (McDermed et aL, 1975;McDermed et aL, 1976;Hacksdl et aL, 1979). Recently, however, an N-substituted monohydroxy aminotetralin, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), has been shown to be a centrally acting selective serotonin (5-HT) agonist devoid of dopamine agonist properties (Arvidsson et aL, 1981).…”

In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist11C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate

“…In order to study the HA-state of the dopamine D2 receptor, we radiolabeled the well-known D2 receptor agonist, 5-OH-DPAT (McDermed et al, 1976;Hacksell et al, 1979). Radiosynthesis of the positron-emitting analog 11 C-5-OH-DPAT was carried out by using 11 Cpropionyl chloride (Shi et al, 1999).…”

“…We have initiated the development of the carbon-11 labeled D2 receptorselective agonist (R,S)-2-(N-N-dipropyl)amino-5-hydroxytetralin (5-OH-DPAT; McDermed et al, 1976) and its analogs. This compound reportedly has a nanomolar affinity for the HA-states of the dopamine D2 receptor (K d ϭ 10 nM for D2 high sites; Seeman et al, 1985).…”