Amarullah H.

Siregar
Jakarta, 8 Juli 2012
Sex occur in response to SEX
Organ
various stimuli. These stimuli are
processed and
integrated
supraspinally
(e.g., medial preoptic
area, paraventricular
The integrated signal
reaches the sex tissues Arousal nucleus) as well as
spinally.
and starts the arousal.
 Various central acting
Dopamine
Dopamine Oxytoxin EAA
EAA

NOS
ACTH/αMSH
ACTH/αMSH M-CCP
M-CCP
Androgen

Arousal
appear to be dependent on nitric oxide as well as androgens
 PHYSICAL PSYCHOLOGICAL
Anemia Depression
Dyspareunia Anxiety
Anorgasmia Too much work
Disease Childhood setback
Substance abuse Past sexual abuse
Alcoholism Homosexualism
Hormonal changes Complicated relationship
Medication Post Traumatic Stress
Obesity Menopause
 Multi factor Female sexual dysfunction
dopamine,
acetylcholine,
and nitric oxide
CHEMICAL INVOLVE
Female
Female Sexual
Sexual Dysfunction
Dysfunction

Sexual
Sexual desire
desire Sexual
Sexual arousal
arousal Sexual pain
Sexual pain Orgasmic disorder
Orgasmic disorder

Hypoactive sexual Inability to attain Dyspareunia: genital Delay in or absence

desire disorder: or maintain an pain associated with of orgasm after a
absence or deficiency adequate lubrication sexual intercourse normal sexual
of sexual interest swelling response excitement phase
Vaginismus:
Sexual Aversion involuntary
Disorder: avoidance contraction of the
of genital contact with perineal muscle
a sexual partner
 ACC, claustrum,
Motivational Comp Post Parietal Cx,
Hypothalam, SN,
Ventral striatum

Emotional Comp SI, SII, Amygdala,

Post Insula

Autonomic and ACC, ant Insula,

Endocrine Comp Potamen, Hypothal

ACC: anterior cingulate cortex; Ant.: anterior; Comp: component; Cx: cortex; Inf.: inferior; IPL/SPL:
inferior/superior parietal lobule; OFC: orbitofrontal cortex; PMv: ventral premotor area; post.: posterior; SI/SII:
primary/secondary somatosensory cortex; SMA: supplementary motor area; SN: substantia nigra.

neurophenomenological model of sexual arousal.

• The PDEs play a central role in regulating smooth muscle tone, and control a wide variety
of physiologic processes and functions. They can be subdivided into enzymes that are
functionally and structurally related, and so far 11 of these PDEs (1-11) have been
identified.[14] Of these, PDE5 has been targeted for ED drug therapy. The PDE5 inhibitors
increase the physiologic response to sexual stimulation by modulating and affecting the
cellular responses responsible for erectile smooth muscle relaxation. Specifically, PDE5
inhibitors inactivate PDEs that normally metabolize the nucleotide cyclic GMP (cGMP). The
accumulation of cGMP allows for an enhanced smooth muscle relaxation and improved
erection through increased blood flow.
• Although some concern has been raised over the cardiovascular safety of sildenafil,
studies show that sildenafil and the second-generation PDE5 inhibitors soon to be licensed
(vardenafil and tadalafil) are safe in most men. In fact, recent studies show that the PDE5
inhibitors may actually improve endothelial function, which is considered the pathologic
process common to both ED and vascular disease. Two studies by Halcox[15] and
Mahmud[16] recently reported that sildenafil improved relaxation of the arteries (ie,
Augmentation Index), improved the constriction response to acetylcholine when endothelial
dysfunction was present in the coronary arteries, and that acute and chronic dosing of
sildenafil increased brachial artery diameter and thus improved endothelial function.
• Other studies also indicate that sildenafil is safe in terms of other cardiac diseases,
including congestive heart failure and myocardial infarction. Katz[17] reported that single
doses of sildenafil (12.5-50 mg) in patients with Grade II/III heart failure resulted in no
major changes in heart rate, blood pressure, or rate-pressure product. Furthermore,
sildenafil in doses of 25 mg and 50 mg improved flow-mediated vasodilation.

central role in regulating

smooth muscle tone
L Arginine A carnitine
Ginseng
Æ
Ashwaganda Depend on Ca++ intracellular
Æ ÆRely on: - cGMP
Genistein Catuaba
- cAMP
- Hyperpolar K+

Vasodilator transmitter
● Nitric Oxide
Æ release from nitrergic
nerve & vasc endothel
- stimulate cGMP
● Vasoactive Intestinal
Coleus Æ Polypeptide (VIP) & PGE1
Rhodiola Æ act Adenylate Cyclase
Damiana
- produce cAMP

cGMP & cAMP

Intercell Ca++
↓
Hyperpolarization K+

Relaxation of cavernosal smooth muscle

 L Arginine Nitric Oxide stimulation
Pasak bumi
Tongkat ali

• Nitric oxide, produced from its precursor L-arginine by nitric oxide synthase (NOS),
appears to exert two effects within the corpora (Figure 17): Nitric oxide exert two
• (1)Activation of potassium-channel ATPase, resulting in hyperpolarization of the
effects within the smooth
corpora
muscle cell membrane. This hyperpolarization prevents the opening of voltage-dependent
(1) Activate K⁺-channel ATPase
calcium channels, thereby reducing intracellular calcium;
(2)Activation of guanylate cyclase which catalyzes the conversion ofÆ hyperpolarization SMC
guanosine
Æ prevents
triphosphate (GTP) to cGMP. This triggers relaxation by lowering intracellular the opening of
calcium.
• Other muscle relaxants act via cAMP-dependent mechanisms and include voltage-dependent
prostaglandin Ca⁺
(PG) E1 and vasoactive intestinal polypeptide (VIP). These substances Æ intracellular
react with calcium ↓;
membrane receptors coupled to a G protein which stimulates adenylate cyclase
(2) Activate to produce
guanylate cyclase
cAMP, thus lowering intracellular calcium. The presence of two distinct and separate
Æ catalyzes guanosine
pathways to induce intracorporeal vasodilatation is probably a reflectiontriphosphate
of the importance
(GTP) to
of the erectile mechanism in the perpetuation of the species.
cGMP.
• The breakdown of cGMP, accomplished mainly
Passion flower by phosphodiesterase type 5 (PDE5),
Æ triggers relaxation by
raises cytoplasmic free calcium levels and reverses smooth muscle relaxation. Compounds
such as papaverine and the recentlyPfaffia panicul more selective, molecule
discovered, lowering intracellular
sildenafil inhibit Ca⁺
Cnidium
intracorporeal PDE5, thereby increasing themon
intracellular half-life of cGMP and, thus,
promoting and prolonging smooth muscle relaxation and erection.
 Norepinephrine
released from dense-
core vesicles of
sympathetic nerve
DMAE terminals
Horny goat Æinteract with α-
Macca adrenoceptors located
• Figure 18 Norepinephrine is released from on cavernosal smooth
muscle membranes
dense-core vesicles in sympathetic nerve
terminals within the corpora. Norepinephrine
The interaction of
norepinephrine with the
then diffuses across the synaptic gapαÆ↑increase
to
-adrenoceptor
in
activate α-adrenoceptors located on the intracellular Ca⁺ via a

cavernosal smooth muscle cell membrane. guanidine nucleotide-

binding protein (G
Second-messenger systems amplify the protein) mechanism
amplified through
signal and induce smooth muscle contraction
inositol phosphate (IP3)
and diacylglycerol
by increasing levels of intracellular calcium.
(DAG) pathways
↑
By contrast, &lpha;-blockers
Shilajit
such as Sympathetic nerve
phentolamine (Vasomax®) interrupt this activity is therefore
involved in both
pathway thereby enhancing penile erection
inducing detumescence
and active maintenance
of intracavernosal

Adrenergic mechanism smooth muscle tone

Stimulation of alpha;-
adrenoceptors on Vitamin B
membranes of smooth Zinc picolinate
• Figure 19 Second-messenger systems
muscle cells
Æ within the corpora
following stimulation of &lpha;-adrenoceptors
Æ involve guanidine
nucleotide binding
on the membranes of smooth muscle cells
protein (G protein)
and phospholipase C
within the corpora involve guanidine
(PLC).
Æ the signal is amplified by
nucleotide binding protein (G protein) and
two pathways
inositol phosphate (IP3)
phospholipase C (PLC). The signal is
& diacylglycerol (DAG)

Increase amplified
level of intracellular by two pathways involving inositol
Lindera
calcium and consequent
phosphate
smooth muscle contraction (IP
Sea ) and
sponge
3
Yohimbe
diacylglycerol (DAG),
respectively. DongThe
Quay result is an increase in the
level of intracellular calcium and consequent
smooth muscle contraction
Alpha adrenoceptor stimulation
Neurohistochemical preparation of a microscopy section through a human pelvic nerve
demonstrates the presence of nitric oxide synthase (staining green)
Neurohistochemical preparation of a microscopy section of dog corpus cavernosum demonstrates
the presence of nitric oxide synthase (a; staining red) and vasoactive intestinal polypeptide (b;
staining green). The two mediators of penile erection are co-localized to a non-adrenergic non-
cholinergic nerve ending
Arousal : ↑ parasympathetic
(originating S2–S4)
Preganglionic neurotransmitter
Æ Acetylcholine
Æ modulate noradrenergic
vasoconstrictor tone
Æ acting upon prejunctional
muscarinic receptors
Postganglionic nerve endings
Æ mediating vasodilation
Æ NANC.
 Release of NO
↓ principal neurotransmitter
accumulation of cGMP mediating trabecular
↓ smooth muscle relaxation
smooth muscle cell relaxation
• Non-Adrenergic Non-Cholinergic ↓ Mechanisms
The principal neurotransmitter mediating trabecular smooth muscle
relaxation is NANC. vasodilatory responses
Originally, the 28 amino-acid peptide VIP was put
forward as the candidate molecule, but it is now recognized that
most nitric oxide
important
(NO) is the most important molecular mediator of erection.molecular
NO synthase
mediator is
present in the pelvic nerves (Figure 20) and in the peripheral autonomic
nerve endings innervatingYohimbe
the corpora (Figures 21 and 22). Release of NO
leads to the accumulation Ginkgo
of cGMP within trabecular smooth muscle cells
and hyperpolarization of the cell membrane. The resultant reduction in
intracellular calcium leadsGinseng
to smooth muscle cell relaxation which, as
already mentioned, spreads rapidly from cell to cell through so-called gap
junctions.
• Vasodilatory responses are terminated by degradation of cGMP, mainly by
the enzyme PDE5.
•
Read more: Mechanisms of erection
http://www.health.am/sex/more/mechanisms-of-erection/#ixzz1xUU4c4DT

Non-Adrenergic Non-Cholinergic Mechanisms

 Borage
Erection ≈ neurovascular event
Æ depends on relaxation of trabecular Primrose
smooth muscle in the corpora cavernosa
and corpus spongiosum
Flaccid state
Æ smooth muscle of the trabeculae
• Penile erection is a neurovascular event that
contracted depends on relaxation of trabecular smooth
Æ bloodmuscle in the corpora cavernosa and corpus
flow is reduced. spongiosum. During the flaccid state, the
smooth muscle of the trabeculae in these tissues and in the blood vessels of the penis is
contracted and blood flow is reduced.
• Tumescence depends on smooth muscle relaxation mediated by cholinergic and
nonadrenergic/noncholinergic mechanisms. There are 2 major signaling pathways. In one,
the release of nitric oxide (NO) stimulates the production of intracellular cyclic nucleotide
cyclic guanosine monophosphate (cGMP).[20] cGMP causes relaxation of the corporal
smooth muscle through a variety of mechanisms, including the reduction of intracellular
calcium.[21] The other signaling pathway also causes smooth muscle relaxation but by
increasing the concentration of the cyclic nucleotide cyclic AMP (cAMP) by stimulating
adenylate cyclase. Among the mediators of adenylate cyclase activity and cAMP formation
Tumescence
in the penile corpora cavernosa are vasoactive intestinal peptide, calcitonin gene-related
Tribulus
peptide, prostaglandin E-1 (PGE-1), and adenosine. The end result again is a decrease ↓ in
intracellular calcium. Epimedium smooth muscle relaxation
• Ferulaof corporal smooth muscle, resulting in rapid
Both pathways bring about relaxation ↓ arterial
filling and engorgement of theCinnamon mediated
sinusoids within the cavernosum, as well by cholinergic and NANC
as venoocclusion,
which results from compression of the subtunical venules against the tunica albuginea.
release NO increasing cAMP
↓ ↓
↑ cGMP ↑ adenylate cyclase
↓ ↓
relaxation VIP,
smooth muscle Calcitonin & PGE-1
 Icariin

Vitex
Black cohosh
Pycnogenol
DHEA

Epimedium
Tribulus
 Vaginal lubrication during sexual activity
Not all / occasionally Frequently Always

100%

80%
Percentile

60%

40%

20%

0%
20-29 30-39 40-49 50-59 60-69 70-79 80+

Age (years)
Arousal disorders
 Chamomile
Quebracho Upleasant
Restore vagina odour
Firms and tightens More pleasure
suppleness the vagina and comfort
Spanish fly

Reduce excessive Women

Release estrogen Stimulating libido
mucus Secret Serum
Schizandra Red clover

Increase vaginal Contracts & reshape Intensify sexual

secretion the walls pleasure
Anise Restore lubrication Asparagus

Solve vaginal
dryness
Parsley