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ECADO in neuromodulation of erection and ejaculation

Private urologist N. Chernobayev

Pavlovsk, Saint-Petersburg, Russia

March 2010

The erectile function is controlled by the autonomous nervous system, which is comprised of two main segments, sympathetic and parasympathetic.

Mediators that act on the cavernous tissues of the penis are different depending on the segment of the autonomous nervous system involved: acetylcholine acts in the parasympathetic synapses (cholinergic), and noradrenaline, in the postganglionic sympathetic synapses (adrenergic). The recent hypothesis implies that the cholinergic nerves do not act immediately on the cavernous bodies but rather modulate some other nervous effector systems (Saenz de Tejada et al., 1988).

Data accumulated so far suggest the existence of an nonadrenergic, noncholinergic nervous transmission (NANC). The generally recognized candidate NANC mediator is vasoactive intestinal peptide, VIP (Virag et al., 1982). VIP-ergic fibers follow the same anatomic pathways as cholinergic fibers do. VIP-ergic fibers are found in both, sympathetic and parasympathetic, postganglionic nerve projections of different segments of the vegetative nervous system. Some data suggest that VIP is a co-mediator involved in joint neuromodulation together with acetylcholine and may be more important than acetylcholine for the initiation of erection [3].

Camphora was known earlier to enhance the reflectory activity of the sacral segments of the spine and to recover it in cases of the spinal shock thus conforming the fact that camphora influences the spinal centers [2].

A significant property of the pharmacodynamics of camphora is its M- and N-cholinolytic activity. Metabolic changes in the sacral segment of the parasympathetic nervous system initiate a chain reaction caused by zonal changes in the excitation state [8]. However, in spite of the M- an N-cholinergic effects of camphora, i.e., the blockage of nervous transmission via cholinergic and adrenergic fibers, its stimulatory action on the spinal centers S2-S4 induces erection. Is it really so paradoxic? Earlier, this phenomenon was explained with the high sensitivity of the parasympathetic erection-controlling center to camphora rather than with its M- and N-cholinolytic effects. Autonomous nerves stimulation causes muscular relaxation in male cavernous bodies in spite of the cholinergic and adrenergic blockage [3]. This confirms a pivotal role VIP-mediated pathways of nervous transmission for triggering of erection. Thus, nerve impulse transmission occurs not only via the cholinergic fibers, as it was believed earlier, but, also, via the VIP-ergic ones.

Parasympathetic responses tend to be localised more narrowly and, one may say, be more prolonged thus facilitating energy conservation in the body. The very essence of the cholinolytic action of camphora is to enhance oxygen consumption implying more energy consumption over a shorter period of time [7]. As early as in 1914, Barcroft has put forward the principle that an increased activity of a body organ is associated with increased oxidative metabolism and blood flow. Camphora enhances metabolic processes in the sacral segment of the parasympathetic nervous system. Thus, under sexual arousal (stress), the alternative pathway of nerve transmission via VIP-ergic fibers becomes the primary one where vasoactive intestinal peptide plays the role of the main mediator, which acts as a co-mediator of acetylcholine.

In the presence of intact endothelium, the cavernous bodies respond to sexual arousal by generation of nitric oxide (NO), which diffuses through cellular membranes into the smooth muscle cell layer. Smooth muscle contraction result in the outburst of NO(Nobel Prize 1998), which act as a signaling molecule in the nervous system upon stress (see diagram). Smooth muscle relaxation caused by NO activates guanylate cyclase, which, in its turn, increases the production of intracellular transmitter of nervous impulses, 3.5-cyclic guanosine monophosphate. It is long known that camphora is able to normalize capillary and venular tone and to restore impaired permeability of capillary membranes. Camphora reliably tones up venous vessels [8]. The effects of camphora on the venous tone is reflectory. Impulses generated upon excitation of chemoreceptors by camphora are transmitted via the afferent pathways to the vasomotor center and from the latter, via the efferent pathways, to vasoconstrictors of the venous wall.

We know that the ejaculation center relates to the sympathetic nervous system and is localized at the level of segments L-3 of the spine. From there, out of the anterior horns of these segments, the sympathetic nerve fibers project to the penis via sexual and pelvic nerves. Nerve impulses generated by the ejaculation center are blocked at the sympathetic ganglia by the N-cholinolytic affect of camphora.

It so happens that advances in the basic knowledge about the neurophysiology of erection and the mechanisms of erection triggering are always facilitated by empirical findings.

This is true for yohimbine, papaverine and Viagra and now, for Ecado. In this section, I will try to provide insight into the effects of Ecado, which was developed based on commonly known camphora, on the neuromodulation of erection and ejaculation. Ecado is the first neuromodulator of erection to immediately act on the sacral center of the parasympathetic nervous system. It provides for a balanced rearrangement of the functional state of the erection center featured by a number of disease conditions. The very effect of the preparation confirms the relevance of VIP-ergic pathways to erection proper. Here I will not consider the other, local, factors of erection that do not relate to neuromodulation themselves.   

The use of Ecado for the neuromodulation of the ejaculatory function is easier to understand as a manifestation of the N-cholinolytic action at the level of spinal ganglia.   

ECADO for male infertility treatment

Several empirical medicamentous therapies for male infertility associated with sperm pathology are available. Each of the therapies has its proponents.

However, non of the methods are rigorously substantiated since non ensure results usually required to assess the efficacy of a drug used (see Table) . The Table comprises data taken from the book by R. G. Pepperel where the author discussed the effectiveness of different therapies for sperm pathology.

The causes of most cases of idiopathic sperm pathology are still unknown so as, consequently, the methods for treatment thereof. Several characteristics of camphora are, to my mind, very important for shedding light on the impressive results (95% of pregnancies achieved) achieved in treating of men having Stage 2 or 3 oligospermia. These characteristics are determined by the high surface activity of camphora and, hence, its ability to be sorbed on surfaces. First, this is the bactericidal activity of camphora. Second, this is its possible blocking activity towards antisperm antibodies. Serum immunoglobulins (IgG and IgA) penetrate into semen plasma in healthy men by transudation, mainly at the level of the prostate [1]. Probably, highly absorbed camphora, according to the Gibbs-Thomson principle, forms solvate envelopes at spermia surfaces and displaces weakly absorbed substances from the surfaces. Spermia are known to have double respiration, aerobic and anaerobic. The main mode of cellular respiration is always aerobic.

One of the main causes of male infertility is believed to be hypoxia resulting from circulatory disorders associated with varicocele, prostatitis, and small pelvis congestion. It is taken for proven that where adenosine triphosphate level decreases, spermia loose their motility [1]. This is preceded by hypoxia. Camphora influences macroergic phosphates metabolism by inhibiting adenosine triphosphate cleavage to adenosine monophosphate under hypoxia, the effect being explained by an increased oxidative resynthesis of macroergic phosphates due to anaerobic glycolysis activation. This is known as the Pascal effect.

ECADO for treatment of benign prostate hyperplasia (BPH) and prostatitis

From ancient times, plant extracts have been being used for treating of prostate diseases. Currently, plant-derived preparations are most popular in Germany, Austria, Switzerland, France, Italy, Spain, and Japan.

Literature provides no data about the pharmacodynamic mechanisms of action of these preparations. This is associated with the peculiarities of local diets with regard to high levels of phytosterols, which afford preventive effects on prostate diseases development.

The lowest prevalence of BPH (adenoma of the prostate) is found in the eastern countries, Japan and China in the first place, and, also, in Africa. After 80 years of age, BPH affects 95.5% of men (Portnoy, 1979). Surely, BPH is inevitable for each men. Thus, prostate diseases are clearly age-associated, inevitable, and virtually ubiquitous. It is for the treatment and prevention of prostate diseases that the preparation Ecado has been developed basing on commonly known camphora. Two forms of the preparation are available: highly dispersed camphora emulsion and camphora-containing rectal suppositories.

The mechanism of action of the preparation is considered primarily from the viewpoint implying colloid protection.

The protective action of the preparation is manifested at the level of biocolloids comprised by the basic substance of the stromal tissue and by prostatic secretion, which under inflammation and at advanced and elder ages change so as to acquire hydrophobic properties associated with colloidoclasia (flocculation and decreased dispersity) [11].

Cell protoplasm is a labile, highly hydrophilic mainly proteinaceous colloid. Stretched polypeptide chains of protein molecules interact to form an intricate molecular net acting as the internal carcass or cytoskeleton.

Its very important property is its extreme motility. Even in its sol state, protoplasm has some internal structure. Protoplasm, nucleus and membranes of all cells are essentially proteinaceous colloidal systems featuring high hydrophilicity. Usually, live tissues contain much water (about 80%); however, all this moisture is bound to colloids (living tissues do not contain free moisture).

The potent enzymic system of the organism depends on the colloidal state of protein bodies. Over lifespan, body colloids undergo changes expressed as decreased hydrophilicity, protective properties, swelling ability and dispersity, which is usual for any aging colloidal system. Colloidoclasia is only a innocuous manifestation of body aging, just as the shortening of telomers, the terminal segments of DNA molecules(Nobel Prize 2009).

The protective effect of camphora is explained with its physicochemical properties, in particular, its high surface activity. According to the Gibbs-Thomson principle, substances that decrease surface tension at an interface of two phases are adsorbed at this surface. The greater is the decrease in surface tension, the higher is adsorption. The quantitative measure of the protective effect of camphora is the so-called "golden number", which defines the minimal amount of camphora expressed as milligrams that prevents the coagulation of prostate secretion.

The prostate is a male inner sex organ. Three groups of glands are distinguished in the prostate. In fact, the age-associated increase in prostate size is cosed by not its total increase, but rather by the adenomatous growth of the periurethral glands. The immediate causes of this adenomatosis are still uncertain. An important role in BPH development is likely to belong to a disturbed colloidal balance in an aging organism. The immediate vicinity of the urethra contains tiny periurethral glands. Each gland opens separately into the urethra. Prostate secretion is generated continually over the whole lifespan.

A small amount of periurethral gland secretion is released more or less perpetually and is mixed with the urine upon urination. Urine flow in the prostatic segment of the urethra generates hydrodynamic pressure and condition for emptying of the glands. The approximate amount os secretion released daily upon urination is 0.5 to 2.0 mL (the so-called basic secretion). The greatest proportion of the secretion is released upon ejaculation. After a certain age, probably 30-35 years, males start to experience significant changes in the prostate, and, as a rule, signs of prostatitis start to develop. In about 40-80% of men, impairments in the copulative function appear.

As men age, the condensed secretion of the prostate is released incompletely. The secretion has altered physicochemical properties. Its viscosity is increased above the norm. The flow of urine passing the prostatic segment of the urethra does not provide for emptying of the periurethral glands. Because their secretion is generated perpetually, their acini are stretched by their thick secretion. In patients, this is palpated as prostate swelling.

The development of BPH proper starts 2-3 years later. The adenomatous, transformed, periurethral glands increase thus compressing the prostatic tissue. Camphora comprised by ECADO is easily absorbed through the rectal wall and is secreted unchanged by prostatic glands with their secretion, which is mixed with it and thus liquifies it. It undisputed that congestion in the prostate is stable. In this way, the congestive prostatitis develops. Thereafter, under congestive prostatitis conditions, infection may be added. As a rule, this is pyogenic microflora including E. coli, Enterococcus, Enterobacter etc.

Many studies aimed to shed light on the causes of prostatitis provided reasons to exclude fungi, obligate anaerobes, trichomonas, viruses, mycoplasma, ureaplasma and chlamydia as etiological factors [10]. Bacterial prostatites are rear. Camphora features high bactericidal activity, the pyogenic microflora being most sensitive to it [8]. The bactericidal activity of camphora is explained with its high surface activity. The development of congestive prostatitis and, as a direct consequence, the age-associated development of BPH, represent the links of one pathogenic chain included in the natural aging process.

ECADO may be used for prophylaxis, and I recommend to start using it after 35-37 years of age. This will help, more or less, to prevent the development of congestion in the prostate and thus to avoid the development and further progression of clinically significant BPH.


The preparation ECADO has the following pharmacological properties:

  • colloid protection;
  • M- and N-cholinolytic activity;
  • capillary poison antagonism;
  • activation of the ejaculation center of the parasympathetic nervous system;
  • normalization of capillary and venular tone;
  • activation of the vasomotor centers of the spine;
  • enhancement of macroergic phosphates synthesis and inhibition of ATP cleavage under hypoxia;
  • analgetic, bactericidal, and fibrinolytic effects; and
  • blockage of nerve impulse transmission from the ejaculation center of the sympathetic nervous system.
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