By Lyle McDonald
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Extra info for Bromocriptine: An Old Drug with New Uses
We only need to worry about two of them: the long form receptor and the short form receptor which are referred to as OB-RL and OB-Rs, respectively. Currently, it looks like the OB-Rs is involved in leptin transport into the brain but the OB-RL is what’s important for leptin to have an effect in all of the other brain areas (19). The DB gene is what tells the body how to make the OB-RL. Because of the defect in the DB gene, the DB mouse only makes the OB-Rs, but not the OB-RL. So while leptin can get into the brain (via the OB-Rs), it has no effect because of the defective OB-RL.
These include an inability to initiate movement, tremor, and other severe neurological defects. The movie ’Awakenings’ with Robin Williams dealt with patients that had Parkinson’s disease. High dose bromocriptine (up to 40 mg per day) along with drugs such as Ldopa (a synthetic dopamine-like drug) and many others are used to deal with Parkinson’s, in an attempt to restore normal functioning. Because of the severe pathology involved in Parkinson’s, as well as the massive doses used, I don’t consider most of the Parkinson’s research to be really relevant for what I’m going to describe.
As with complete leptin deficiency, only a very few cases of complete leptin resistance have been found in humans. The FA mouse has only a partial defect in the leptin receptor. So leptin can send a signal, just not a very good or strong one. The FA mouse is partially leptin resistant which is a lot closer to what goes on in humans (unlike the DB mouse). Finally there is the DIO rat, a rat made fat with a poor diet and no exercise. As it gets fatter, it becomes leptin resistant and its setpoint goes up so that it defends higher and higher bodyfat levels.