Cabergoline 2012

When Cabergoline, which is the derivative of ergot, is on the D2 receptors it is a potent dopamine receptor agonist. It's brand names are Cabaser and Dostinex. The study of rats in Vitro shows that the inhibitory effect on the cells known as pituitary lactotroph (prolaction) was direct. Its affinity for the receptor sites of D2 is high and that is why it is mainly used as a first line agent to manage prolactinomas.
In 1981/82 the scientists who were working in Milan invented Cabergoline; these scientists were working in a drug company, which was owned by Italy, called Farmitalia-Carlo Erba Spa. They were experimenting with derivatives of ergot alkaloids which were semisynthetic. In 1992 Pharmicia acquired Farmitalia-Carlo and in 2002 Pfizer in turn acquired this company. The FDA approved the drug on December 23, 1996 and when the US patent expired in the late 2005, this drug became generic.

A patent application for the Cabergoline was filed by Farmitalia in 1982, and in July 1985 the U.S Patent 4,526,892 was issued.

Cabergoline has a significant affinity for the receptors of α2B-, 5-HT2C, 5-HT2B, 5-HT2A, 5-HT1A, D4 and D3 even though it is described mainly as the agonist of the dopamine D2 receptor. It has low to moderate affinity for the receptors of the 5-HT7 and D1. In all the receptors, Cabergoline is an agonist however it is an antagonist in α2B- and 5-HT7.

The resorption of the Cabergoline from the tract known as gastrointestinal (GI) is usually variable after a single dose is taken orally and this usually occurs within 0.5 hours to 4 hours. The absorption rate will not be altered if it is ingested with food. The drug is only for oral use that is why the human bioavailability has not been determined. The absolute bioavailability in both mice and rats has been determined, in mice it is 30 percent and 63 percent in rats. In the liver, Cabergoline is mobilized extensively and rapidly and it is excreted in bile. It is excreted in small quantities in urine. The metabolites are inactive or less active than the parental drug. The half-life of the human elimination has been estimated to be 63 hours to 68 hours and this for those patients who have the Parkinson's disease and for the patients suffering from the pituitary tumors; it is estimated to 79 hours to 115 hours. The average of the half-life elimination is 80 hours.

When hyperprolactinemia is being treated, the effects of therapeutic usually persist for more than four weeks after stopping the treatment.

Cabergoline is an agonist of dopamine D2-receptor and it acts for a long time. The studies of rats in vitro show the direct inhibitory effect which affects the secretion of the prolactin in the lactotroph cells of pituitary. In the reserpinized the levels of the serum prolactin is usually decreased by Cabergoline.

The studies of the receptor-binding indicate it has low affinity for the receptors of dopamine D1, α1-adrenergic and α2-adrenergic.

The Uses of Cabergoline
It used in hyperprolactinemiar
Adjunctive therapy of the pituitary gland, which produces prolactin, tumors prolactinomas;
Monotherapy in the early phase of the Parkinson's disease;
Combination therapy in the progressive-phase of the Parkinson's disease, the decarboxylase inhibitor like carbidopa is combined with levodopa;
Also in some countries: ablactation and the dysfunctions from hyperprolactinemia (galactorrhea, nonpuerperal mastitis, anovulation, oligomenorrhea and amenorrhea);

Used in the treatment of the uterine fibroids.

The adjunctive therapy of acromegaly. The efficiency of cabergoline to suppress level of the growth hormone is very low and the efficiency to suppress the hyperprolactinemia which is present in the 20% to 30% of the cases of acromegaly is very high. The structure of both prolactin and the growth hormone is the same and their effects on the target tissues are also the same. Therefore, it may help the symptoms when prolactin is targeted when the secretion of the growth hormone cannot be controlled sufficiently by other methods;
Cushing disease - cabergoline is usually used in lowering the levels of ACTH and in causing the regression of the pituitary adenomas which produces ACTH;
Other pituitary adenomas - cabergoline has been known to be efficient when used to control or to reduce the other types of the pituitary adenomas, and the non-functional or silent adenomas.

The Recreational use or Off-label

Cabergoline has been known to counteract certain side effects of the SSRI, which are anorgasmia and reduced libido, which is why it has been used many times as an adjunct to this drug. There are suggestion online which suggests that cabergoline can be used for recreational purposes such as to reduce or eliminate the refractory period of males, this will allow men to experience multiple ejaculatory orgasms and in rapid succession. There is one scientific study which supports the speculations. The bodybuilders uses it in controlling the gynecomastia and which is caused when the levels of the prolactin is elevated when the bodybuilder uses anabolic steroids like Trenbolone and Nandrolone. Also, there is a systemic review and meta-analysis which concluded that treating prophylactic with cabergoline helps in reducing the incidence and not the severity of the ovarian hyperstimulation syndrome (OHSS), and the pregnancy outcomes will not be compromised, in the females who are going through the stimulated cycles of the in vitro fertilization (IVFO). There is also a study of rats which shows that cabergoline helps in reducing the voluntary alcohol consumption and it is possible because it increases the expression of GDNF in ventral tegmental area.