Anaesthetic properties of phencyclidine (PCP) and analogues may be related to their interaction with Na+ channels.

Among other properties, phencyclidine (PCP) and analogues display anaesthetic and anticonvulsant properties. Interaction of PCP and some analogues with the voltage-sensitive Na+ channels have been investigated and compared with their interaction with the PCP receptor. PCP and TCP inhibit apparently in a competitive manner the veratridine stimulated 22Na+ synaptosomal uptake with Ki values of 8.6 and 12.7 microM, respectively, close to those obtained in the inhibition of [3H]BTX-B binding (IC50 = 4.1 and 3.8 microM, respectively). The specific [3H]TCP binding to synaptosomes in ionic near physiological conditions is inhibited by PCP and TCP with IC50 values of 1.25 and 0.29 microM, respectively. Other PCP derivatives (GK3 and GK4) and PCP-like drugs (ketamine and MK801) inhibit 22Na+ uptake in an order of potency (GK3 greater than GK4 greater than PCP greater than TCP greater than MK801 greater than ketamine) which is different from that obtained in the inhibition of [3H]TCP binding (MK801 greater than TCP greater than PCP greater than ketamine greater than GK4 greater than GK3). Ketamine inhibits the veratridine-stimulated Na+ uptake at a concentration where its anesthetic effect occurs. It was concluded that the interaction of these drugs with the Na+ channel may reflect their anaesthetic properties while the interaction with the PCP receptors may be mainly related to their anticonvulsant and ataxic properties.