Cerebral dopamine agonist properties of some 2-aminotetralin derivatives after peripheral and intracerebral administration

Abstract

A series of variously N-substituted 2-aminotetralins having OH groups at 5 and 6 and at 6 and 7 positions, as well as nonoxygenated systems, has been evaluated for central dopaminergic effects. Stereotypical behavioral effects (sniffing, compulsive gnawing, and hyperactivity) produced by direct intracerebral administration of some of the agents were shown to differ strikingly from responses resulting from peripheral administration. The centrally mediated responses of hyperactivity and sterotypical gnawing-biting head and limb movements were shown to be separable in some test compounds. An improved route to 2-aminotetralin systems has been utilized for some of the compounds, which involves Pummerer rearrangement and cyclization of beta-keto sulfoxides and reductive amination of beta-tetralones with a NaBH4-carboxylic acid complex.

Pharmacological Evidence for the Subclassification of Central Dopamine Receptors in the Rat

“…The weaker action of apomorphine intracerebrally suggests that the drug may have a more restricted access to appropriate receptors when injected by this route. As in other reports, (Cannon, Lee, Goldman, Costall & Naylor, 1977;Makanjuola, Dow & Ashcroft, 1980) we found that dopamine receptor agonists required a considerable time, 1-2 h, to reach peak effect following intracerebral injection, suggesting a slow rate of diffusion to active sites. In this context, apomorphine may diffuse less readily than other agonists following localised injection into brain tissue.…”

A Concise Synthesis of 2‐Amino‐1,2,3,4‐tetrahydronaphthalene‐6,7‐diol (‘6,7‐ADTN’) from Naphthalene‐2,3‐diol

“…Cannon et al [9] described the second method for the preparation of 2 starting from ethyl 3-(3,4-dimethoxyphenyl)propanoate. Horn et al [10] developed a procedure for the synthesis of 2 starting from (3,4-dimethoxyphenyl)acetic acid.…”

(S)-5,6-Dimethoxy-1,2,3,4-tetrahydro-2-naphthalenamine– L-(+)-Mandelic Acid (1/1): the Absolute Configuration of a Precursor of the Active Stereoisomer of 5,6-ADTN, an Important Dopaminergic Agonist

“…Racemic 5,6-ADTN has been synthesized in many laboratories (McDermed et al, 1975;Horn et al, 1978;Sprenger, Cannon, Barman & Burkman, 1969;Mitsuhashi, Adachi, Shimizu, Nomura & Shiotani, 1972;Cannon & Costal, 1977), but none of the synthetic routes seem to be suitable on a multigram scale owing to their overall low yield. To overcome this difficulty, we studied an alternative route which does not require any purification by chromatography and which gives an improved overall yield.…”