PMID- 15821157
OWN - NLM
STAT- MEDLINE
DCOM- 20070720
LR  - 20131121
IS  - 1534-0384 (Print)
IS  - 1534-0384 (Linking)
VI  - 5
IP  - 2
DP  - 2005 Apr
TI  - Mechanism of tissue-selective drug action in the cardiovascular system.
PG  - 84-93
AB  - Analysis of the human genome project tells us that there may be as few as 3000 
      genes that are likely to be good drug targets. Although the number of targets is 
      still very large, these data have been interpreted by some to mean that the 
      pharmaceutical industry may someday run out of novel drug targets. Despite the 
      doom and gloom of such analysis, there is considerable reason for optimism. Drugs 
      may exhibit selectivity of action beyond that predicted by target expression 
      alone. Drugs that act at a single molecular target may have very different 
      pharmacology and, as a result, different therapeutic uses. Three 
      well-characterized model systems are highlighted to illustrate this point. The 
      first model system is exemplified by nifedipine and verapamil, both of which act 
      on L-type calcium channels. Both drugs are used to treat hypertension, but only 
      verapamil can be used to produce atrioventricular block in patients with atrial 
      fibrillation. The second model system describes the therapeutic exploitation of 
      unusual conditions that occur in the ischemic myocardium to produce drugs that 
      are more effective for suppressing ischemia-induced arrhythmias. The third model 
      system discusses the mechanisms through which phosphodiesterase-5 (PDE5) 
      inhibitors act selectively to facilitate penile erection while having little 
      effect in the non-penile vasculature that also expresses PDE5.
FAU - Barrett, Terrance D
AU  - Barrett TD
AD  - Department of Physiological Systems, Johnson & Johnson Pharmaceutical Research & 
      Development L.L.C., San Diego, CA, USA. TBarret1@PRDUS.JNJ.COM
FAU - Triggle, David J
AU  - Triggle DJ
FAU - Walker, Michael J A
AU  - Walker MJ
FAU - Maurice, Donald H
AU  - Maurice DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Mol Interv
JT  - Molecular interventions
JID - 101093789
RN  - 0 (Calcium Channels)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - CJ0O37KU29 (Verapamil)
RN  - EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterases)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5)
RN  - EC 3.1.4.35 (PDE5A protein, human)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - 3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors
MH  - Binding Sites
MH  - Calcium Channels/chemistry
MH  - Cardiovascular System/*drug effects
MH  - Chemistry, Pharmaceutical/methods
MH  - Cyclic Nucleotide Phosphodiesterases, Type 5
MH  - Electrophysiology
MH  - Erectile Dysfunction/drug therapy
MH  - Humans
MH  - Hypertension/drug therapy
MH  - Ischemia/drug therapy
MH  - Male
MH  - Models, Anatomic
MH  - Models, Biological
MH  - Myocardium/pathology
MH  - Nifedipine/pharmacology
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Verapamil/pharmacology
RF  - 29
EDAT- 2005/04/12 09:00
MHDA- 2007/07/21 09:00
CRDT- 2005/04/12 09:00
PHST- 2005/04/12 09:00 [pubmed]
PHST- 2007/07/21 09:00 [medline]
PHST- 2005/04/12 09:00 [entrez]
AID - 5/2/84 [pii]
AID - 10.1124/mi.5.2.6 [doi]
PST - ppublish
SO  - Mol Interv. 2005 Apr;5(2):84-93. doi: 10.1124/mi.5.2.6.