General anesthetics-Medicinal Chemistry

Definition, Classification, mechanism of action, Structure activity relationship, synthesis and uses of General anesthetics

1. Dr. Gopal Krishna Padhy

2. “General anesthetics are CNS depressant drugs that induce

absence of perception of all sensations and loss of pain.
# They depress the CNS non selectively but reversibly.

4. A

Cyclopropane
)

N,O

Nitrous oxide

C2H5—-O-CoHs

Diethylether

5. Y

| Barbituric acid derivatives |

LN +
\—sna

NH

6. Ketamine

Hydrochloride

7. H2F2/ SbCl,
A ————

0
Trichloroethylene LEURS

MOA: Halothane causes

Bra, 450 °C
CF3CH2-CI ————>

2-chloro-1,1,1-
trifluoroethane

anesthesia due to its actions on

multiple , which ultimately

, ’

. Its effects have

been attributed to its binding to in

cholinergic neurons. Halot

binding to receptc

Uses: Halothane is a mo

ane's effect are also likely due to

or and , causing

ern and widely used

. It is used in both short and long-lasting surgical

operations. It acts very quicl

and it is very safe.

kly, which is pleasing to patients,

8. : a+ H_ COOC;Hs
432 CHsONa

+ CoHs-C2C-CH- CyHs—C=C-CHCOOC Hs

Hf SCOOC;Hs ICh; CHs

Diethyl malonate 2-Bromo-3-hexyne H! a

H, COOC;H, + H,C=CH-CH,-

20H50

o o
H2C=CH=CHa yy \ N HyC=CH-CH JL oc,Hs
=0 OX + Ñ

NH N CHs-C=C-CH Te
CH

CaHs-C=C-GÍ
CH; ©
Ho] NaOH
Y

o
H¿C=CH—Ch

9. Y

Mechanism of action of methohexital

“It is believed that methohexital decreases the electrical
nerve activity in the CNS that leads to general anesthetic
action.
%* Methoxehital binds to

complex. This binding of GABA
for the GABA, receptor.
“It leads to via an

increase in the frequency of the chloride channel opening. At

higher dose, it directly increase conductance of Cl ion and

calcium dependant

10. “In addition to above it also depress glutamate induced
neuronal depolarization through AMPA receptor. At very high
dose barbiturates depress Na* and K* ion channels also.

Uses:

It is primarily used to induce anesthesia. It is only used in

hospital under strict supervision. It has been used to induce

deep sedation for surgery and dental procedure.

11. CC

2-ohlorobenzonitrilß, clopentyl magnesium
bromide

j oe
NHCHa — o, “ii

Ketamine

12. Reaction mechanism for step-5

13. Mechanism of Action

“*Ketamine show multiple therapeutic properties like
,

c and effects by acting

on different sites.

#N-methyl-D-aspartate (NMDA)-receptor antagonism is the

most important neuropharmacological mechanism for the
effects of ketamine.
«e Effects on opiate receptors may contribute to the
proporties as well as to dysphoric reactions.
properties are mediated by enhanced

central and peripheral monoaminergic transmission.

14. “Inhibition of central and peripheral cholinergic transmission
may contribute to the induction of anaesthetic state and
hallucinations.

Uses:

Ketamine is a specific drug for non-inhalation anesthesia. It is

used in brief surgical procedures. It is indicated as the sole

anesthetic agent for diagnostic and surgical procedures.

15. MOA: Enflurane
positive of
the GABA, receptor. It also
inhibits receptor activity in the
NMDA
subtypes. These yield a decreased

acts as a
glutamate receptor

and therefore,

depolarization

tissue excitability which results
in anesthesia.

Uses: Used for the induction
and maintenance of general
anaesthesia during surgery and as

analgesia during child delivery.

MOA: Similar to enflurane.
Used for the
induction and maintenance

Uses:
of general anaesthesia
during surgery and cesarean
section and also used for
child

analgesia during

delivery.

16. MOA: Similar to enflurane.

Uses: Used for the induction
and maintenance of general
anaesthesia during surgery and
child

for analgesia during

delivery.

MOA: Similar to enflurane.

Uses: Used for the induction
and maintenance of general
anaesthesia during surgery

and cesarean section and also

used for analgesia during

child delivery.

17. -0-CH, F

MOA: Similar to enflurane.

Uses: Used for the induction
and maintenance of general
anesthesia during surgery
and also as analgesia during

child delivery.

C2Hs
H3C-CH,-CH2—CH
CH

MOA:
methohexital sodium.

Similar

Uses: Thiopental is an
extremely short
barbiturate that
pleasant and

acting
makes
anesthesia
smooth for the patient. It

has been used to induce

deep sedation for surgery

and dental procedure. “~~

18. H¿C=CH-CH)

CH,-CH¿-CH2-GH
CH;
MOA: Similar to

methohexital sodium.

Uses: It has sedative, hypnotic
and anticonvulsant properties
and is used as a short acting
sedative. It is used primarily

for induction of surgical

anesthesia or as an
anticonvulsant to counteract
side effects from other

anesthetics.

19. Wilson and Gisvold, Text book of organic, Medicinal

and Pharmaceutical Chemistry.

«e Foyes Principles of medicinal chemistry by Williams
O. Foye.

*% A Text book of medicinal chemistry (Synthetic and
Biochemical Approach) vol. I& II by SN Pandeya.

“Synthesis of Essential Drugs by R.S. Vardanyan and
V.J. Hruby