Anticholinergic effects of cis-chlorprothixene characterized in rat parotid acini.
The anticholinergic effects of the antipsychotic drug, cis-chlorprothixene, on the secretory events underlying the formation of primary saliva were investigated. The neuroleptic, cis-chlorprothixene, is used extensively as a major tranquillizer but shares side-effects such as xerostomia with most antidepressants. The inhibitory effects of cis-chlorprothixene upon the cholinergic-induced rise in Ca2+ as well as on O2 consumption and Cl- loss were investigated in isolated rat parotid acini in order to characterize its anticholinergic effects quantitatively. The cholinergic-induced rise in cytosolic, free Ca2+ was inhibited by cis-chlorprothixene with half-maximal effect at 1.9 microM and maximal inhibition at 10 microM. When the cytosolic, free Ca2+ was enhanced in the presence of 10 microM cis-chlorprothixene by means of the Ca2+ ionophore A23187, a loss of Cl- was observed similar to that observed during cholinergic stimulation in the absence of cis-chlorprothixene. The findings are consistent with the possibility that cis-chlorprothixene exerts its effects on the steps leading from agonist binding to the acetylcholine receptor and to the increase of cytosolic free Ca2+. Thus, measurement of the stimulation-induced rise in cytosolic, free Ca2+ in the presence of neuroleptics such as the thioxanthenes represents a fast and reliable method for detecting inhibitory effects on autonomic receptor activation.
Undén
M
M
Department of Psychiatry 2, Sankt Hans Hospital, Roskilde, Denmark.
Nauntofte
B
B
Dissing
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D002749:Chlorprothixene / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010276:Parasympatholytics; D010306:Parotid Gland / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D010276:Parasympatholytics; D002217:Carbachol; D002749:Chlorprothixene; D002118:Calcium