CNS stimulant
Used in treatment of depression and as analeptics.
I. Analeptics
Drugs enhance the response to sensory stimulation
Respiratory stimulant
1 .Nikethimide
Et
Et
N
N
O
2 .Ethamivan
OCH3
C2H5
C2H5N
O
OH
3 .Methylxanthines
Caffeine Theophylline Theobromine
N
NN
NO
R1
O R3
R2
II. Antidepressants
MAO inhibitors TCAs Miscellaneous
A. MAO Inhibitors Elevate biogenic amine by inhibiting MAO.
hydrazine Non hydrazine
Iproniazide Tranycyprominephenelzine
1. Iproniazide
S.E
N
NHONH
CH3
CH3
Hydrazine derivative
2. phenelzine
NH
NH2
Non hydrazine derivatives
Less SE
Tranylcypromine
NH2
B. Tricyclic antidepressants (TCAs)
SAR Side effects
anticholinergic effects
N
N
R
R
1. Imipramine hydrochloride (tofranil)
Close relative to antipsychotic phenothiazines SE: anticholinergic and sedative efffects
(CH2)3 N
N
CH3
CH3
2 .Desipramine hydrochloride
(CH2)3 NH
N
CH3
.HCl
3 .Amitriptyline hydrochloride
NCH3
CH3
.HCl
4 .Nortriptyline
5. Doxepin hydrochloride
Oxacongener.
O
N
CH3
CH3
.HCl
C. Miscellaneous
Effects on cardiovascular system.
NH
CH3
1 .Maprotiline hydrochloride
2.Trazodone hydrochloride
Similar to fluorobutyrophenone 5HT SE: sedation
NN
N N
N
O
Cl
3. Fluoxetine
Serotonin reuptake inhibitor
F3C
NHCH3O
III. psychadelics
Local anesthesia
Characteristics for an ideal local anaesthetics
- reversible blockade of sensory nerve fibers with a minimal effect on the motor nerve activation
Toxicity and side effects Effects on excitable membranes such as in the
heart, the neuromuscular junctions, and the CNS. With more effect on neuromuscular junctions and the CNS.
convulsions, followed by severe CNS depression, (particularly of the respiratory and cardiovascular centers). Due to inhibtion of inhibtory neurons as GABA system.
amide-type local anesthetics likely to produce CNS side effects than the ester- type compounds
SE depend on route and site of administration, the lipid solubility and metabolic stability of local anesthetics.
allergic reactions rare
More with p-amino-benzoic ester-type amide- type: antiarhythmic (parenterally and at
a subanesthetic dosage) effect on Na channel.
SAR Lipophilic portion
NH2
C O CH2 CH3
O
H2N+
C O CH2 CH3
O -
Intermediate chain
- Short alkyl (1-3) carbons- Nature of chain determine stability and
duration (amide more resistant)- Branching increase the duration
• hydrophilic portion
Tertiary alkyl amine form water soluble
Classification
Ester type Amide type
Ester type procaine
NH2
ON(C2H5)2
O
Procaine
• benzocaine
NH2
O
O CH2CH3
Benzocaine
• Tetracaine
C4H9 NH
ON(C2H5)2
O
Tetracaine
• benoxinate
C4H9
NH2
ON(C2H5)2
O
O
Benoxinate
Amide type Lidocaine
CH3
CH3
NH
N(C2H5)2
O
Lidocaine
CH3
CH3
NH
O
NCH3
Mepvacaine
Synthesis of lidocaine
CH3
CH3
NH2
+Cl
ClO
CH3
CH3
NHCl
O
NH
CH3
CH3
Lidocaine
Metabolism
Ester type esterase interaction with anticholinesterase increase toxicity
Antagonize the antibacterial activity of sulfonamide
Amide type: