Cabergoline, trade names Dostinex and Cabaser, is a very potent Dopamine Receptor (D2) agonist with inhibitory effects on prolactin. Cabergoline is primarily used to treat prolactinomas, benign tumors of the pituitary gland that result in overproduction of prolactin. Prolactin is involved in post-coital satiety, breast lactation, and - depending on amount and timing - increased receptor susceptibility to luteinizing hormone in the Leydig cells of the testicles. Dopamine's inverse relationship with prolactin levels is best exemplified by the arousal/satiety cycle: dopamine is partially responsible for sexual arousal, and after orgasm prolactin is partially responsible for sexual satiety and non-arousal.
Cabergoline has not been shown to interact with coadministered selegiline or levodopa; as a dopamine receptor agonist it has potential for treatment of Parkinson's disease. However, a lack of direct interaction with selegiline or levodopa does not mean one should infer a lack of complication from excessive dopamine levels, which is a particular concern any time multiple dopamine agonists or pro-dopamine chemicals are used in conjunction. Cabergoline is only FDA-approved for indication for hyperprolactinemia/prolactinomas, not for Parkinson's or related ailments, although off-label use is documented and under study.
A primary concern of practitioners is the association between cabergoline and valvular heart disease, which does not necessarily mean that cabergoline causes valvular heart diease; Vallette et al write:
Ergot-derived dopamine receptor agonists, especially pergolide and cabergoline, have been associated with an increased risk of valvular heart disease in patients treated for Parkinson's disease. Cabergoline at lower doses than those employed in Parkinson's disease is widely used in patients with prolactinomas, because of its high efficacy and tolerability; however, its safety with regard to cardiac valve disease is unknown. ...Our results show that low doses of cabergoline seem to be a safe treatment of hyperprolactinemic patients. However, in patients with prolonged cabergoline treatment, we suggest that echocardiographic surveillance may be warranted.
Where cabergoline successfully treats prolactinomas, combined therapies may still be required to achieve other desirable therapeutic outcomes (such as fertility):
we report a case of macroprolactinoma in a 36 year-old infertile man who failed to attain normal serum testosterone level and fertility on either bromocriptine or cabergoline. Testosterone replacement or human chorionic gonadotropine (hCG) therapy in this patient resulted in a rise of prolactin (PRL) levels, which declined following therapy discontinuation. The combination of high doses of bromocriptine, hCG and an aromatase inhibitor facilitated near normalization of PRL levels, shrinkage of adenoma, recovery of serum testosterone level, sexual function, sperm count and achievement of fertility. CONCLUSION: aromatase inhibitor may facilitate successful testosterone replacement therapy in male patients with prolactinoma.
M.R. Safarinejad reports promising results using cabergoline to "salvage...sildenafil failure," with sildenafil and similar drugs likely remaining a first line of pharmaceutical treatment for erectile/sexual dysfunction due to fewer and less serious side-effects as well as (within the study mentioned) lower incidence of patient-elected discontinuation of the drug for all reasons, including side-effects.
Cabergoline is occasionally used to treat acromegaly. Verhelst, Abrams ,and Abs report that "acromegalic patients with a good response to cabergoline may occasionally remain in remission after stopping therapy."
Regarding acromegaly treated with cabergoline, Lombardi and Colao write:
The treatment of acromegaly and hyperprolactinaemia has been improved by the availability of effective and well-tolerated slow-release somatostatin analogues and dopamine agonists with long-lasting activity, such as cabergoline. The use of these drugs has extended the possibility of treatment to patients who would have responded poorly to the previously available compounds, such as octreotide or bromocriptine, and to those who were intolerant to pharmacotherapy. Moreover, the improvement in the management of acromegaly has enabled the reversal, at least partly, of cardiomyopathy and sleep apnoea, two important risk factors for morbidity and mortality in these patients.
Finally, a novel and promising study on cabergoline from Carnicella et al, whose findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders.
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