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Interaction
Introduction:
The vast majority of drugs show a remarkably high
correlation of structure and specificity to produce
pharmacological effects. Experimental evidence
indicates that drugs interact with receptor sites
localized in macromolecules which have protein-like
opposite charges.
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Finally hydrophobic bonds are formed between nonpolar hydrocarbon groups on the drug and those in
the receptor site. These bonds are not very specific
but the interactions do occur to exclude water
molecules.
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allosteric site.
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Receptor Down-regulation: Is a
phenomenon whereby an agonist , actually
induces a decrease in the number of those
receptors available for binding.
Receptor up-regulation: Is a phenomenon
whereby an agonist , actually induces an
increase in the number of those receptors
available for binding.
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D+R
DR
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Macromolecular perturbation theory: Suggests that when a drugreceptor interaction occurs, one of two general types of
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Other theories
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DRUG LATENTIATION:
TYPES
Carrier-Linked Prodrugs
Bioprecursors
result from an in vivo molecular
modification of the drug itself
(e.g. sulindac, cyclphosphamide)
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Drug
Chemical synthesis
+
Temporary
Transporter
(Carrier)
Regeneration in vivo
Prodrug
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IN VIVO
METABOLISM
+ CH2=O
+ CH3C(CH3)2COOH
O
CHCNH
NH2
O
AMPICILLIN ( AMPICIN, PENBRITIN)
S
N
Me
Me
+ CO2
+ CH3CHO
+ CH3CH2OH
COOH
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DRUG
ACTIVE METABOLITE
acetanilide
acetaminophen
imipramine
desipramine
L-DOPA
dopamine
phenylbutazone
oxyphenbutazone
chloral hydrate
trichloroethanol
proguanil
cycloguanil
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sulindac
reductive bioactivation
of sulindac
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cholesterol
targetor
spacer
peptide
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YAGFL
enzymatic release
of peptide
YAGFL
enkephalin
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Prodrug =
Drug Latentiation
OH
OH
O
HO
NHMe
NHMe
HO
O
Dipivaloyl ester
Epinephrine
In vivo
Poor corneal penetration
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CCH3
CCH3
COO
CH-O-C-O-C2H5
Bacampicillin
CH3
Me
CH2- O- C C Me
O
Pivampicillin
Me
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CH2
OR
C
Me
HO
CH3
O
O
Me
CH3
acetonide
F
O
F
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2. To Patient Acceptability :
OH
CHCl2
N
O
O2N
OH
H
CHCl2
N
O2 N
O
(CH)14CH3
O
ester
Chloramphenicol
( Bitter taste )
Chloramphenicol Pamitate
(without Bitter taste )
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CH3 O
N
H
N
O
CH3 O
N
R
NH2
HOOC
NH2
Cl
H2N
invivo amidase
CH3 O
N
(Water soluble)
Cl
in
vi v
cy
za
cli
n
tio
Diazepam
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Salt
ester
O
CH2-O
Na+ -O C
P O-Na+
O-Na+
Chloramphenicol Succinate
Chloramphenicol Phosphate
CH2-OH
O
OH
HO
CH2-O-C-CH2CH2COO_Na+
OH
Water soluble
R = - C -CH2-CH2-COO-Na+
Sodium Succinate
O
O
Prednisone
O-Na+
R = -P
O-Na+
O
R = -C-CH3
Acetate ester
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CH2-CH-COOH
CH3
Naproxen (Anti-inflammatory)
COO CH
CO-CHO(CH2)11CH3
Diglycerides Ester
5. To Prolong Duration of
O
Haloperidol : R = H
R=
(CH2)8-CH3
S
N
Decanoate Ester
CF3
N CH2 CH2
OR
Fluphenazine: R = H
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O
C
HO
O
Acetyl Salicylate: R =
RO
H2N
AcO
C O
Naltrexone : (R = H)
HO
O
O
CH3
OH
Terminal ileum
O
N
H
O
N
H
Active oxyphenisatin
"bowel sterilant"
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OH
OH
O
P
HO
OH
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OH
O
N
NH2
O
in Brain
H2N
OH
Cl
GABA
Progabide
BBB
C X- Drug
N
N
Me
C X- Drug
C X- Drug
Metabolism
+
N
(Oxidase)
Me
Me
(locked in brain)
Hydrolysis
COOH
Active drug
Lipophilic
+
N
Me
Trigonelline
( nontoxic)
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H3N CH2-CH2-CH2-COON
GABA
BBB
C NH CH2-CH2-CH2-COO-C6H11
In vivo Cleavage
{ esterase}
Me
GABA
(Lipophilic)
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H
N
Carrier
CH3
CH3
O
O
N
O
S
Brain
C
X
Oxidation
N
Linker
CH3
CH3
CH3
O
N
C
C
X
N
CH3
( Highly hydrophilic )
Locked in brain
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