Importance of polyunsaturated acyl chains in chlorpromazine interaction with phosphatidylserines: A 13C and 31P solid-state NMR study

Etiopathogenesis of metabolic syndrome in schizophrenia – recent findings

“…S obzirom na to da je nedavno pronađeno da u stanicama humanih monocita inzulin inducira aktivnost enzima D6-i D5-desaturaza koji sudjeluju u sintezi PUFA-a iz prekursorskih molekula linolne kiseline (LA; 18:2n-6) i alfa-linolenske kiseline (ALA; 18:3n-3) unesenih prehranom, inzulinska bi rezistencija mogla dodatno pogoršati postojeći deficit PUFA-a u shizofreniji 87 . Bilo bi zanimljivo spomenuti da novije spoznaje proizašle iz in vitro studija ukazuju na mogućnost da bi smanjena koncentracija PUFA-a u membranama pacijenata sa shizofrenijom mogla imati za posljedicu i slabiji terapijski učinak atipičnih antipsihotičnih lijekova 88,89 . Naime, istraživanja su pokazala da su atipični antipsihotici amfifilne molekule koje se ugrađuju u unutrašnji (citosolni) dio fosfolipidnog dvosloja, a čini se da molekule PUFA ubrzavaju proces njihove ugradnje olakša-vajući interakciju lijekova s membranskim glicerofosfolipidima.…”

Fat Intake and CNS Functioning: Ageing and Disease

“…They have produced strong molecular evidence using solid-state magic angle spinning 13 C-NMR, demonstrating the drug interacts not with proteins of the receptor but with the brain phosphatidylserine. Further studies with pure 18: 0/22: 6n-3-phosphatidylserine showed that chlorpromazine reduced the mobility of the C4 and C5 atoms in DHA, which are attached to each other with a double bond [Chen et al, 2005].…”

An intercalation mechanism as a mode of action exerted by psychotropic drugs: results of altered phospholipid substrate availabilities in membranes?

“…The data prove that the drugs studied affect the three above-mentioned metabolic phenomena (PPI cycle, PLA 2 / arachidonate metabolism, and MLC phosphorylation) via intercalation into phospholipids of the inner leaflet of the cell membrane. Solid-state 13 C-and 31 P-NMR studies have disclosed the interaction between CPZ and PS liposomes at the atomic level where the positive charge in the CPZ tail amino group makes an ionic bond with the phosphate-and carboxyl groups of PS, while the tricyclic lipophilic phenothiazine moiety is embedded among the acyl groups [34,127]. It has also been proposed that the therapeutic potentials of anesthetics (which are also cationic amphiphiles) are proportional to their solubility in the lipid/ aqueous interface [139].…”

“…As a future complementary method, to strengthen the theory of intercalation of psychotropic drugs in-between membrane phospholipids, solid-state 13 C-and 31 P-NMR should be undertaken also with the remaining 16 psychotropic drugs used in the work discussed in this review, where the cationic amphiphilic drug (CPZ) has shown to interact with PS. Fluidity of cell membranes including neurons, is secured by PUFAs in sn-2 acyl positions of membrane phospholipids, this is needed for normal metabolism and cell functions besides PUFAs enhance efficacy of psychotropics [25,160] via facilitating their intercalation inbetween acidic glycerophospholipids [34]. Since many of these PUFAs are essential fatty acids, they must be taken into the human body through the diet, implicating the importance of nutritional habits in the society.…”