N-docosahexaenoyl, 3 hydroxytyramine : A dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite

Fatty Acid Derivatives of Clozapine Prolonged Antidopaminergic Activity of Docosahexaenoylclozapine in the Rat

“…Given these pharmacological properties, DHA-clozapine or similar agents should be evaluated as potential antipsychotic drugs with improved central/peripheral distribution, and possibly enhanced safety that requires verification in clinical trials. Moreover, the principle represented in linking a known centrally active drug with a fatty acid carrier molecule such as DHA as a means of enhancing CNS distribution and activity may be applicable to other compounds of neuropsychopharmacological interest, including hydrophilic agents that poorly penetrate the blood-brain barrier (Jacob et al 1985;Shashoua and Hesse 1996).…”

“…As a strategy aimed at testing this hypothesis, we followed our previous findings with ester or amide derivatives of fatty acids important in the composition of brain tissue, including some that are effectively transported into the central nervous system (CNS). Such derivatives can markedly enhance entry of some compounds into the brain, including hydrophilic agents such as GABA and dopamine (Jacob et al 1985;Shashoua and Hesse 1996). Accordingly, we considered preparing derivatives of clozapine and fatty acids that are abundant in brain tissue but must be supplied exogenously and transported through the blood-brain barrier.…”

“…Docosahexaenoic acid (DHA) is a particularly interesting candidate for attachment to clozapine because it is vigorously transported into the CNS and accounts for a high proportion of cerebral fatty acid content (Söder-berg et al 1991;Martin et al 1994). Moreover, in earlier work, DHA proved particularly effective in facilitating entry of hydrophilic compounds into the brain (Shashoua and Hesse 1996).…”

Synthesis of a novel class of fatty acids-derived isoquinolines

“…The uptake of the xenobiotic molecules into the brain could be greatly facilitated by linking them to the lipophilic part of a substance that normally is able to pass through blood-brain barrier due to its amphiphilic character (a carrier molecule). Particularly, the amide derivatives of fatty acids (bioactive fatty acid amides) were specified as a new class of lipid bioregulators (Shashoua and Hesse, 1996;Bezuglov et al, 1997). Even simple long-chain amides like Nacylethanolamines (anandamides) exhibit a wide range of biological activity including the role as the endogenous cannabinoids (Hillard et al, 1995).…”

Antioxidant and neuroprotective properties of N-docosahexaenoyl dopamine

“…N-Docosahexaenoyl dopamine (DHX-DA) increases the content of dopamine and its metabolites in the brain tissue in rodents [8]. Acylated form of biosynthetic dopamine precursor N-linolenoyl tyrosine also increases brain dopamine concentrations and produces an antiparkinsonic effect in rats with experimental Parkinson's disease [5].…”