Antagonistic effects of dextromethorphan on vasoconstriction of phencyclidine in vitro

Bioassay and spectrophotofluorometry were used to study the antagonistic effect of dextromethorphan (DM) on phencyclidine (PCP) vasoconstriction in rabbit ear artery. DM (5 mumols.L-1) antagonized enhancement of PCP, N-[1-(2-thienyl) cyclohexyl] piperidine (TCP) and dizocilpine maleate (MK-801) (5 mumols.L-1) on electrical stimulation-induced vasoconstriction by 86 +/- 18%, 84 +/- 17%, and 86 +/- 18%, respectively (n = 6, P less than 0.01), but had no obvious bioactivity itself at the same concentration. DM (1, 2.5, and 5 mumols.L-1) inhibited the PCP effect and reduced the maximal effect of PCP with pD2' = 5.3 +/- 0.3 (n = 4). The contents of norepinephrine (NE) in control, PCP, and DM + PCP groups were 5 +/- 6, 12 +/- 8, and 5 +/- 6 ng.ml-1, respectively (n = 9). PCP (10 mumols.L-1) increased the NE release (P less than 0.05) but DM (10 mumols.L-1) inhibited it (P less than 0.01). The results suggest DM may be a noncompetitive blockader for PCP receptors.