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Vol. 53, Issue 3, 417-450, September 2001
Department of Clinical Pharmacology, Lund University Hospital,
Lund, Sweden
I. Introduction
II. Central Regulation
A. Central Mediators
1. 5-Hydroxytryptamine.
2. Dopamine.
3. Noradrenaline.
4. Excitatory Amino Acids.
5. 
-Aminobutyric Acid.
6. Oxytocin.
7. Adrenocorticotropin and Related Peptides.
8. Opioid Peptides.
9. Acetylcholine.
10. Nitric Oxide.
III. Peripheral Regulation
A. Contraction-Mediating Transmitters/Modulators
1. Noradrenaline.
2. Endothelins.
3. Angiotensins.
B. Relaxation-Mediating Transmitters/Modulators
1. Acetylcholine.
2. Nitric Oxide and the Guanylyl Cyclase/cGMP
Pathway.
a. Nitric-Oxide Synthases.
b. Soluble Guanylyl Cyclases.
c. Cyclic GMP-Dependent Signaling.
3. Vasoactive Intestinal Polypeptide.
4. Prostanoids.
5. ATP and Adenosine.
6. Other Agents.
a. Adrenomedullin and Calcitonin Gene-Related
Peptide.
b. Nociceptin.
C. Impulse Transmission
1. Electrophysiology.
2. Gap Junctions.
3. Signal Coordination.
D. Excitation-Contraction Coupling
1. Ionic Distribution.
2. K+ Channels.
a. The KCa Channel.
b. The KATP Channel.
3. L-Type Voltage-Dependent Calcium Channels.
4. Chloride Channels.
5. Contractile Machinery.
a. Contraction.
b. Relaxation.
IV. Pharmacology of Current and Future Therapies
A. Erectile Dysfunction
Risk Factors
B. Drugs for Treatment of Erectile Dysfunction
C. Drugs for Intracavernous Administration
1. Papaverine.
2. 
-Adrenoceptor Antagonists.
a. Phentolamine.
b. Thymoxamine.
3. Prostaglandin E1 (Alprostadil).
4. Vasoactive Intestinal Polypeptide.
5. Calcitonin Gene-Related Peptide.
6. Linsidomine Chlorhydrate.
D. Drugs for Nonintracavernous Administration
1. Organic Nitrates.
2. Phosphodiesterase Inhibitors.
3. Prostaglandin E1.
4. K+ Channel Openers.
5. -Adrenoceptor Antagonists.
a. Phentolamine.
b. Yohimbine.
6. Opioid Receptor Antagonists.
7. Dopamine Receptor Agonists.
a. Injected Apomorphine.
b. Oral Apomorphine.
8. Trazodone.
9. Melanocortin Receptor Agonists.
V. Conclusions
Acknowledgments
References
Erection is basically a spinal reflex that can be initiated by
recruitment of penile afferents, but also by visual, olfactory, and
imaginary stimuli. The reflex involves both autonomic and somatic
efferents and is modulated by supraspinal influences. Several central
transmitters involved in the erectile control have been identified.
Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as
oxytocin and adrenocorticotropic/-melanocyte-stimulating hormone, seem to have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. Peripherally, the balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora
cavernosa and determines the functional state of the penis. Noradrenaline contracts both corpus cavernosum and penile vessels via
stimulation of 1-adrenoceptors. Neurogenic NO is
considered the most important factor for relaxation of penile vessels
and corpus cavernosum. The role of other mediators released from nerves or endothelium has not been definitely established. Erectile
dysfunction (ED) may be due to inability of penile smooth muscles to
relax. This inability can have multiple causes. However, patients with ED respond well to the pharmacological treatments that are currently available. The drugs used are able to substitute, partially or completely, the malfunctioning endogenous mechanisms that control penile erection. Most drugs have a direct action on penile tissue facilitating penile smooth muscle relaxation, including prostaglandin E1, NO donors, phosphodiesterase inhibitors, and
-adrenoceptor antagonists. Dopamine receptors in central nervous
centers participating in the initiation of erection have been targeted
for the treatment of ED. Apomorphine, administered sublingually, is the
first of such drugs.
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