402 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1952 



substances in early commercial lots of penicillin resulted in specifica- 

 tions by the Armed Forces, who during World War II procured all 

 of this drug, which required animal tests to demonstrate the absence 

 of pyrogenic substances. Likewise, safety tests in mice were included 

 to eliminate the possibility that chance contamination with solvents 

 and other materials might render the product harmful. 



The doses utilized, even in early clinical trials of penicillin, were 

 relatively high and were a direct indication of the extremely low 

 toxicity of this drug. At the present time, doses as high as 100,000,000 

 units daily of crystalline sodium or potassium penicillin G are given 

 without untoward effects. There is little or no pain following intra- 

 muscular injection of crystalline penicillin. However, early lots of 

 amorphous penicillin of low purity were quite painful on injection. 

 As a matter of fact, there was a significant correlation between the 

 purity (potency) of commercial sodium penicillin and irritation fol- 

 lowing intramuscular injection. With an increase in potency in units 

 per mg., there was a corresponding decrease in the pain produced. 



The early indications were that penicillin produced no serious toxic 

 effect on the nervous system. However, there is no question now, that 

 even with the pure crystalline drug, nerve tissue is vulnerable to its 

 action. Convulsions may follow intraventricular administration of 

 penicillin in man and can be induced in animals by direct application 

 of penicillin to the cerebral cortex. Neurological complications in 

 patients with pneumococcic meningitis have been noted after 

 intrathecal administration of penicillin. In these cases, neurological 

 symptoms were manifest between the tenth and twenty-third day after 

 the institution of therapy. Both motor and sensory disturbances were 

 observed although recovery was eventually complete. Peripheral 

 neuritis has also been reported as a complication of intrathecal penicil- 

 lin therapy. Localized peripheral neuritis with motor and sensory 

 disturbances has been observed following intramuscular administra- 

 tion of penicillin. Recovery from the neuritis occurs in most cases. 

 Symptoms following intrathecal administration of penicillin, such 

 as listlessness, headache, nausea, vomiting, respiratory difficulty, 

 cyanosis, fall in blood pressure, thready pulse, and muscular twitch- 

 ing, are apparently reduced or eliminated when the dosage is dimin- 

 ished. This is particularly true if barbiturates are used concomitantly 

 with reduction in the dose. When 5,000 units of crystalline penicil- 

 lin are applied to the occipital cortex in human beings, no clinical or 

 electroencephalographic abnormalities occur, whereas 20,000 units 

 of the same material produce definite encephalographic changes. In- 

 dications are that the intrathecal reactions are related to the size of the 

 dose rather than to the concentration, acidity, or alkalinity of the solu- 

 tion used. The irritating effect of penicillin on the central nervous 



