Thomas H. Maren

Acetazolamide treatment of hypokalemic periodic paralysis. Probable mechanism of action.

Following administration of glucose and insulin to three patients with hypokalemic periodic paralysis, serum K+ fell 1.9 mM. After administration of acetazolamide, 250 mg four times daily, serum K+ fell 0.9 mM, a substantial difference. In normal persons glucose and insulin lowered serum K+ 0.5 mM, and this was not changed substantially by acetazolamide. The metabolic acidosis induced by the drug appears to be responsible for the change in decrement of serum K+ and for the amelioration of symptoms in the patients. The findings agree with earlier reports that metabolic acidosis lowers the rate of entry of K+ into muscle, thus opposing the heightened or pathological entry of K+ into muscle cells during attacks of the disease.

The effect of acetazolamide on the transport of potassium and rubidium into guinea pig diaphragm.

Acetazolamide, a potent carbonic anhydrase inhibitor, has been shown to be effective in the treatment of the familial periodic paralyses (1, 2), diseases exhibiting sporadic bouts of flaccid muscle paralysis usually accompanying fluctuations in plasma K+. Current studies in this laboratory indicate that humans treated with acetazolamide (250 mg q. 6 hr) have a lowered potassium entry rate from plasma into red blood cells and other large tissue pools of K+ probably muscle. We have turned our attention to muscle uptake of potassium both in vitro and in vivo, following acetazolamide. Although carbonic anhydrase has never been found in muscle, these experiments were still indicated because of at least two possibilities: (a) that the enzyme was present in amounts less than we or others could detect, and (b) that an effect in vivo was secondary to systemic or metabolic effects of acetazolamide, i.e., the production of metabolic or respiratory acidosis. This possibility is particularly relevant since acidosis following NH4Cl (3) or CO2 (4) does result in lowered net K+ entry into muscle. Methods. Male guinea pigs (200-500 g) were sacrificed by decapitation. Diaphragms were removed and quickly transferred to a petri dish of warm Tyrode solution through which a mixture of oxygen and 5% CO2 was bubbled. Diaphragms were sectioned into strips of approximately 15 mg, and aponeuroses, endplate and rib cage attachments were carefully removed. All muscle strips were incubated for 30 min in 37° Tyrode solution, using the same CO2 gas mixture, to allow for potassium leakage due to mechanical injury of the muscle. Strips of muscle were separated randomly into two groups and incubated in fresh media for 30 min. For the treated group, the medium also contained acetazolamide, 1.5 × 10-4 M.

Condensation of 2,3-Dimercaptopropanol (BAL) with Oxophenarsine Hydrochloride: Toxicity and Chemotherapeutic Effect

Summary 1. The condensation product of BAL and oxophenarsine hydrochloride (BAL-OXO) was studied. Its toxicity in mice and chemotherapeutic activity in T. equiperdum is reported, in comparison with similar data, for oxophenarsine hydrochloride. 2. The acute toxicity of the thioarsenite, BAL-OXO is approximately 1/4 that of the arsenoxide (oxophenarsine hydrochloride) from which it was prepared. 3. The BAL-OXO has less therapeutic advantage, i.e., lower LD50/CD50, in mouse trypanosomiasis than oxophenarsine hydrochloride itself.