The lack of utility of the rat vas deferens as a functional bioassay for sigma ligands.
The present study examined the utility of the rat vas deferens preparation as a bioassay for sigma site ligands. sigma Ligands such as (+/-)-pentazocine, phencyclidine (PCP) and (+)-SK&F 10047 potentiated neurogenic twitch contractions. However, neither the order of potency nor the absolute potency of (+/-)-pentazocine and (+)-SK&F 10047 correlated with their affinity at central sigma sites. Furthermore, another potent sigma ligand, ditolyl-ortho guanidine (DTG) neither affected neurogenic twitch contractions nor inhibited twitch potentiation by PCP or (+)-SK&F 10047 at concentrations up to 30 mumol/l. These data indicate that the rat vas deferens is not a useful bioassay for the evaluation of sigma ligands. PCP, (+)-SK&F 10047 and (+/-)-pentazocine probably enhance neurogenic contractions in rat vas deferens primarily by inhibition of the neuronal uptake of noradrenaline.
Fox
P K
PK
Department of Pharmacology, Organon Laboratories Limited, Newhouse, Lanarkshire, U.K.
Connick
J H
JH
Hanlon
G M
GM
France
L
L
Nicholson
C D
CD
D000818:Animals; D001665:Binding Sites; D001681:Biological Assay; D004558:Electric Stimulation; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010423:Pentazocine / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000187:drug effects*
D006146:Guanidines; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine