About mode of action of carbamate insecticides

1. CARBAMATE INSECTICIDESS
 The carbamate insecticides exits as esters of carbamic
acid, typically have some kinds of aryl substituent as the
leaving group.
 These compound are mot soluble in organic solvents.
 other carbamates are more aliphatic in nature and may
posses sufficient miscibility with water to act as effective
plant systemic insectiides.
O
R1
OCN
R3 R2

2. DEVELOPMENT OF CRBAMATE
INSECTICIDES
 In the 17th century the natives of the old calabar region of
southeast Nigeria, the Effiks, used the coffee-coloured beans,
physostigma venenosum in witchcrafts .
 The crushed bean called ‘esere’ was used as a poison ordeal to
establish the guilt of a poisoner
 Later the alkaloid was isolated , purified and renamed
physostigmine.
 During the same time miotic and cholingeric properties of
physostigmine were discovered.
 The molecular structure was established in 1925 and the
compound was synthesized in 1945.

3.  Stedman elucidated the structure of physostigmine and also
synthesized a number of synthetic analogues of
methylcarbamates some of which were toxic to many insect
species.
 Aeschlimann and Reinert synthesized the corresponding active
and stable dimethylcarbamate which is nestigmine.
 Hans Gysin and co-workers discovered the insecticidal
properties of N-dimethylcaramates in the late 1940s and
synthesized a number of analouges including dimetan , dimetilan
, isolan, pyramat, pyrolan etc.

4.  These compounds though were highly toxic to aphids and
house flies possessed only limited toxicity towards others
insects and due to narrow spectrum of toxicity could not be
introduced commercially.
 At about the same time Metcalf and co-workers modified the
structure of simple phenylmethyl carbamates to increase their
lipid solubility
 They discovered that substation in the ortho or meta position
with alkyl group or a halogen in a phenyl methylcarbamate
increased its insecticidal activity.

5.  They suggested three major requirements for optimum contact
insectidal activity of a carbamate molecule:
1. It should be nonpolar, to be able to penetrate to the site of
action in the insect nerve,
2. It should be structurally complementary to the active surface of
cholinesterase, both in stereochemistry and reactivity, to
effectively inhibit the enzyme; and
3. It should possess sufficient stability to multifunction-oxidase
detoxication

6.  They synthesized a series of nonpolar substituted phenyl
methylcarbamates with insecticidal activity, but first commercially
successful crbamte, carbaryl was synthesized by union carbide
corporation .

7.  In the early 1960s it was found that carbamoyl oximes of cyclic
ketones possessed, in addition to insecticidal properties,
acaricidal and nematicidal properties.
 This led to the synthesis of trisubstituted acetaldehyde O-oximes
which was structurally similar to acetylcholine.
 Aldicarb, an open-chain carbomoyloxime, was subsequently
synthesized.

8. MODE OF ACTION
 Carbamate insecticides, like the organophosphorus compound,
inhabits acetyl cholinesterase by acting as a substrate for
enzyme, resulting in the accumulation of acetylcholine in the
nerve synapse and causing a disruption of nerve function.
 When a carbamate insecticide enters the synapse, it
completes with acetylcholine for the active site on the enzyme.
 The insecticide binds to the enzyme and forms a complex
 The enzyme which is inhibited by OP insecticides is
considerably less susceptible to hydrolysis as a result
regeneration of the free enzyme is slow and recovery from OP
poisoning is a much slower process.

9.  The carbamates react with series hydroxyl group within the
enzymes active site, resulting in carbamylation of this hydroxyl
and group and yielding a hydroxylated “leaving group”.
 This group inactivates the enzyme and blocks the degeneration
of the neurotransmitter acetylcholine.

10. IN INSECTS
 Hyperactivity
 Incorodinated movements
 Convulsions
 Erratic tremors

11. ANTIDOTE
 Atropine antagonizes activity of acetylcholine