Factors in the lethality of i.v. phencyclidine in conscious dogs.

1. Pretreatment were pancuronium prevented convulsions and hyperthermia, but had no effect on acidemia or changes in cardiovascular parameters after intravenous (i.v.) infusion of phencyclidine (PCP). 2. While dogs survived higher amounts of PCP, they failed to regain spontaneous respiratory function. 3. Mechanical ventilation alone increased the mean lethal dose/time of PCP and reduced the effects of PCP on arterial systolic pressure, cardiac output, and PCO2. 4. EKG showed ventricular arrhythmias, which progressed to death. 5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm. 6. Blocking of convulsions prevented hyperthermia and acidemia; respiratory support reduced circulatory effects, but respired dogs then died, at higher doses, from a primary myocardial toxicity of PCP.

Conformationally restrained fentanyl analogues. 2. Synthesis and analgetic evaluation of perhydro-1,6-naphthyridin-2-ones.

Conformational flexibility of the N-acyl portion of fentanyl-type analgetics was restricted through the synthesis of novel perhydro-1,6-naphthyridin-2-one derivatives. Neither the cis-fused derivative (5a), the trans-fused derivative(5b), nor the enamide 8a possessed analgetic activity in the mouse tail-flick assay, reaffirming the sensitivity of this portion of 4-anilidopiperidine analgetics to conformational restraint.