and our knowledge of the allowable diversity 
of R!; CH30-CgH; 70; CH3S-CgH17S; CH3NH- 
C4HgNH, CH3-C,H = >50, 
2h, : i: 
R?: CH30-C3H70; CH,S-C,H_S; 
CH3-CgHy, 7 = 50, 
and the displaceable group X: more than 10,000 
different moieties incorporating electron with- 
drawing groups or groups that can be enzy- 
matically activated to this state (50 x 50x 
10,000 = 25 million combinations), it appears 
that at least 25 million potential insecticides 
can be fabricated around this simple phos- 
phorylating structure. Within this enormous 
framework and fortified with some basic con- 
cepts of the nature of insecticidal specificity 
between mammals and insects, parasites and 
hosts, and susceptible and resistant organ- 
isms, planned organic synthesis shouldbe able 
to achieve almost any desirable goal. 
Selectivity of Carbamates 
These compounds are esters of N-methyl or 
N,N-dimethylcarbamic acid and a variety of 
phenols and heterocyclic enols. Like the organ- 
ophosphorus insecticides they are inhibitors 
of cholinesterase, but because of their close 
spatial similarity to acetyl choline they may 
also have a direct stimulating effect on acetyl 
choline receptors. 
The carbamates are among the most selec- 
tive of all insecticides both in their differential 
toxicity to insects and vertebrates and intheir 
specific action among the arthropods. One of 
the interesting features of this specificity is 
the pronounced effect of formal charge of the 
molecule in preventing insecticidal action. 
Prostigmine while extremely toxic to mam- 
mals is inactive as a contact insecticide, al- 
though it is a very active inhibitor (I5g 2x 
10-8 M) of both insect and mammalian choli- 
nesterase. However, its uncharged carbon 
isosteres, such as m-isopropylphenyl and 
m-tert-butylphenyl N-methylcarbamates, are 
toxic to both insects and mammals (table 8). 
A considerable amount of study has indicated 
that cationic compounds, such as prostigmine 
and acetyl choline, are unable to penetrate the 
lipoid sheath that surrounds insect nerves. 
However, in mammals these compounds, al- 
though they may not penetrate the central 
nervous system, act peripherally where they 
block neuromuscular transmission and cause 
death by respiratory impairment. The failure 
Table 8.--Selectivity of some carbamate insecticides 
[LDso mg. per kg. | 


Insecticide 
m-Dimethylaminophenyl N,N-dimethylcarbamate 
methobromide (prostigmine).............00- 
m-Isopropylphenyl N-methylcarbamate......... 
o-Isopropylphenyl N-methylcarbamate......... 
o-Isopropoxyphenyl N-methylcarbamate........ 
1-Naphthyl N-methylcarbamate (carbaryl)..... 
2-Methyl-2-methylthiopropionaldehyde oxime 
Nemethylcarbamavter | ccc ccc cc cc ssasc sce cis 
1-Isopropyl-3-methyl-S-pyrazclyl N,N-di- 
mebhylicarbamacen (soOilan)) iaepeepseeierearcciele dc 
17 







Musca, | Blattella,|} Apis, Rat, Rabbit, 
topical topical topical! oral dermal 










