Carbamazepine affects neutrophil function through an action on peripheral benzodiazepine receptors.
The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)1 in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to investigate neutrophil function and pBZr expression in patients with epilepsia on CBZ monotherapy for at least 1 year. In vitro CBZ (42-168 microM) concentration-dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C. albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 microM, per se ineffective) reversed the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP. The pBZr agonist Ro 5-4864 (10-100 microM) mimicked the effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs on neutrophils. These data strongly suggest an involvement of pBZrs in mediating the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same neutrophil function parameters and overexpression of pBZrs in patients are consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.
Caldiroli
E
E
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
De Ponti
F
F
Cosentino
M
M
Marino
F
F
Fietta
A M
AM
Taddei
M
M
Tartara
A
A
Zibetti
A
A
Mazzone
A
A
Lecchini
S
S
Frigo
G M
GM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001570:Benzodiazepinones / Q000494:pharmacology; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011963:Receptors, GABA-A / Q000187:drug effects*
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002220:Carbamazepine; C037850:PK 11195