It can also have adverse effects on the cardiovascular system. AAS like methyltestosterone stimulate erythropoiesis (red blood cell production) and increase hematocrit levels and at high dosages can cause polycythemia (overproduction of red blood cells), which can greatly increase the risk of thrombic events such as embolism and stroke. With long-term treatment, AAS can increase the risk of benign prostatic hyperplasia and prostate cancer. Violent and even homicidal behavior, hypomania/mania, depression, suicidality, delusions, and psychosis have all been associated with very high dosages of AAS. Interactions
Aromatase inhibitors can be used to reduce or prevent the estrogenic effects of methyltestosterone and 5α-reductase inhibitors can be used to prevent its potentiation in so-called "androgenic" tissues and thereby improve its ratio of anabolic to androgenic activity and reduce its rate of androgenic side effects. Antiandrogens like bicalutamide and cyproterone acetate can block both the anabolic and androgenic effects of AAS like methyltestosterone. Pharmacology
Pharmacodynamics
As an AAS, methyltestosterone is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT). It is a substrate for 5α-reductase like testosterone, and so is potentiated analogously in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland via transformation into the more potent AR agonist mestanolone (17α-methyl-DHT). As such, methyltestosterone has a relatively low ratio of anabolic to androgenic activity, with a similar ratio to that of testosterone (close to 1:1), and this makes it among the most androgenic AAS.
Other side effects of unknown frequency include reduction in leukocytes, reduction in platelets, reduction in neutrophils, which can lead to increased infections including lung infections; severe allergy-like reactions that can lead to angioedema and skin reactions; lethargy; liver complications including jaundice and abnormal liver function tests; reproductive effects including reduction in sperm count and ovarian failure.When combined with ethanol, procarbazine may cause a disulfiram-like reaction in some people.It weakly inhibits MAO in the gastrointestinal system, so it can cause hypertensive crises if associated with the ingestion of tyramine-rich foods such as aged cheeses; this appears to be rare.Procarbazine rarely causes chemotherapy-induced peripheral neuropathy, a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs. Pharmacology
Procarbazine works, in part, as an alkylating agent and methylates guanine at the O-6 position (much like dacarbazine also does). Guanine is one of the four nucleotides that makes up DNA. The methylated DNA is prone to breakage, and RNA and protein synthesis is inhibited. Proliferating cancer cells need to replicate their DNA and undergo programmed cell death (apoptosis) in response to DNA strand breaks. Normal or non-proliferating cells are more apt to repair the DNA damage, but still some of the healthy cells will be damaged. Procarbazine is metabolized in the liver to an azo-derivative and then further metabolized by the cytochrome P-450 system to an active azoxy-derivative. References
External links
MOPP Treatment Regimen
PCV Information
Procarbazine Drug Information Provided by Lexi-Comp – Merck Manual
RX Listing for Matulane
"Procarbazine".