ATLA::Alternatives to Laboratory Animals

Volume 25, Number 5

The effects of two new amphetamine-like derivatives on the phagocytic ability of the protozoan, Tetrahymena pyriformis.

ATLA 25, 547-553, September/October 1997

Giorgos Alevisopoulos,¹ Maria Stefanidou,¹ Margarita Pagou,¹ Theodora Siatra-Papastaikoudi² and Antonios Koutselinis¹

¹Department of Forensic Medicine and Toxicology, School of Medicine and ²Division of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, 75 M. Asias St., Goudi, 11527 Athens, Greece

SUMMARY

Six new amphetamine-like molecules (2-[2,3-dihydro-4H-1,4-benzoxazine-4-yl] -1-methyl-2-[1-methyl-2-phenylethylamino] ethanamines) were synthesised and their physicochemical behaviour was studied. The log P values (index of lipophilicity) of the derivatives were calculated according to Rekker's fragmental system. One derivative representative of each series (C-5508 and C-5512) was selected, and their biological effects on the phagocytic ability of the protozoan, Tetrahymena pyriformis, were studied as a basic functional test for an amphetamine-like action. Furthermore, the action of both derivatives when administered concomitantly with haloperidol was also investigated. The data indicate that both derivatives significantly increased the phagocytic ability of the protozoan (p < 0.001), presumably via an alternative pathway to that of one of the dopamine monoaminergic pools. The administration of halopendol significantly suppressed phagocytosis (p < 0.001). However, cultures exposed to the derivatives and to haloperidol indicated quantitatively different reactions. The lipophilic behaviours of the derivatives provide a possible explanation for such distinct effects.

Keywords: amphetamines, haloperidol, lipophilicity, protozoan, Tetrahymena pyriformis