EFFECT OF 1-CYCLOHEXYLAMINO-2-PROPYLBENZOATE (CYCLAINE) AND OTHER LOCAL ANESTHETIC AGENTS ADMINISTERED INTRAVENOUSLY ON THE CARDIOVASCULAR-RESPIRATORY SYSTEMS OF THE DOG

¹ Pharmacology Section, The Research Division, Sharp and Dohme, Inc., West Point, Pa.
² Munch Research Laboratories, Inc. Upper Darby, Pa.

Of the several compounds studied, neither procaine nor Cyclaine produced more than a transient effect on blood pressure, heart rate or respiration when administered intravenously in doses of 4 to 5 mgm./kgm. to anesthetized dogs. At dosages of 1 to 5 mgm./kgm. neothesin, cocaine and butacaine produced profound falls in blood pressure, tetracaine induced respiratory failure and dibucaine caused fibrillation and death.

Procaine, Cyclaine, neothesin, cocaine and dibucaine administered by venoclysis to unanesthetized dogs generally increased heart rate and the negative potential of the T-wave of the EKG. Usually the R-wave was decreased and the deflection of the S-wave was increased.

The severity of the effects of any of the agents was a function of dosage. Although the effects on the EKG noted for procaine were essentially similar to those reported previously (Wilburne and Uhley, 1948; Uhley and Wilburne, 1948; Carter and Eisaman, 1950), they seem of such little consequence for either agent (procaine or Cyclaine) as not to influence their acceptability for intravenous administration. It will be recalled that procaine has been used together with massage to induce cardiac function following ventricular fibrillation or asystole of a duration of minutes (Lampson et al., 1948; Roualle, 1950). Since untoward depressor effects occasionally are noted to follow procaine venocylsis (Edmonds et al., 1949), this reaction would seem a more important, though infrequent, complication of therapy.

Procaine and Cyclaine were administered safely over the greatest dosage range. Whereas the convulsion-producing close of procaine was about three times greater than that for Cyclaine, the initiation of excitement in the dogs was at a dosage that was at least as low for procaine as for Cyclaine. Thus it might be anticipated that excitation produced by procaine would preclude its clinical use in unanesthetized patients at dosages exceeding those for Cyclaine. Present evidence indicates that in the presence of anesthesia procaine and Cyclaine produce no profound net cardiovascular-respiratory effects at dosages that preclude the safe administration of neothesin, cocaine, dibucaine, tetracaine or butacaine by venoclysis.

On the other hand, the lack of an anticipated substantially greater per kilo intravenous toxicity of procaine. Cyclaine and neothesin for the dog than for the rabbit indicates a species difference in handling or response to the agents. This observation suggests that caution should be exercised in the transposition of these dosages to human patients or to veterinary practise on larger animals.