ACEA-1328, AN NMDA RECEPTOR ANTAGONIST, INCREASES THE POTENCY OF MORPHINE AND U50,488H IN THE TAIL FLICK TEST IN MICE

The effect of 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was examined on opioid-induced antinociception in the tail flick test. Swiss Webster mice were injected with ACEA-1328 either alone or in combination with morphine or (±)-trans-U-50488 methanesulfonate (U50,488H), a μ- and a κ-opioid receptor agonist, respectively, and tested for antinociception. Systemic administration of ACEA-1328 alone increased the tail flick latencies with an ED₅₀of approximately 45 mg kg⁻¹. Concurrent administration of ACEA-1328 with morphine, or U50,488H, at doses that did not affect tail flick latencies, potentiated the antinociceptive effect of the opioid analgesics and vice versa. Naloxone, an opioid receptor antagonist, while not modifying the effect of ACEA-1328, did block the augmentation, suggesting that opioid receptors might be involved in the latter effect. 5-Aza-7-chloro-4-hydroxy-3-(m-phenoxyphenyl)quinoline-2(1H)-one (ACEA-0762), a selective NMDA receptor/glycine site antagonist, also showed enhancement of the antinociceptive effect of morphine and U50,488H. However, concurrent administration of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), a selective non-NMDA receptor antagonist, with morphine did not alter the antinociceptive potency of the opioid analgesic. Overall, the data suggest that ACEA-1328 may increase the potency of the opioid analgesics by antagonising the glycine site associated with the NMDA receptor.     

Interaction Between Accessory Pathways Resulting in Inability to Induce Reciprocating Tachycardia

A 44-year old male with Wolff-Parkinson-White syndrome presented with atrial fibrillation. The patient was found at the electrophysioiogical study to have two accessory pathways, one concealed and the other conducting exclusively in the anterograde direction. After radiofrequency catheter ablation of the anterograde conducting pathway, orthodromic reciprocating tachycardia, which previously could not be induced despite an aggressive protocol, was easily induced. Ablation of the concealed pathway resulted in termination of the tachycardia and suppression of inducibility. We propose that interaction between the two accessory pathways resulted in an inability to induce reciprocating tachycardia.     

Radiofrequency Modification of Atrioventricular Conduction by Selective Ablation of the Low Posterior Septal Right Atrium in a Patient with Atrial Fibrillation and a Rapid Ventricular Response

A case is presented of a 58-year-old woman with atrial fibrillation and uncontrolled ventricular responses up to 180 beats/min despite therapy with digoxin. Radiofrequency energy was applied to the low posteroseptai right atrium in an attempt to modify "slow fiber" conduction. This resulted in a decrease in ventricular rate from 125 to 50 beats/min. Follow-up Holter monitor demonstrated an average heart rate of 64 beats/min (range 43–112). On exercise tolerance test, the maximum heart rate was 126. Modification of the low posterosepta right atrium may prove to be an alternative to AV node or His bundle ablation and pacemaker implantation in patients with poorly controlled atrial fibrillation and rapid ventricular response. The mechanism by which this approach was effective may be ablation of slow conducting AV nodal fibers with a short refractory period.