Posted by Christ_empowered on May 21, 2016, at 21:36:20
In reply to Re: Dopamine antagonism » linkadge, posted by J Kelly on May 21, 2016, at 17:35:12
hi. Here's the story....
The first antipsychotic--trade name: Thorazine--was originally used in pre-operative sedative cocktails. Using Thorazine at low doses meant lower doses of opiates and barbiturates, which meant fewer problems with suppressing breathing and less time recovering from sedation. Now, the patients treated with Thorazine seemed calm and a bit indifferent, but not slowed down...so...
...they used it in asylums. First lower doses, then higher doses, then they did studies using wide ranges of doses. Eventually, Thorazine was approved as the first tranquilizer with the ability to help schizophrenic and manic patients. The effect was initially referred to as a "chemical lobotomy," because when Thorazine worked, it worked like an ideal lobotomy: the patient was calmer, but not over-sedated, and they gradually lost interest in their psychotic processes.
From day 1, it was apparent that Thorazine could induce Parkinson's-type symptoms, so it obviously had an effect on dopamine. Turns out...whether or not Schizophrenia and other psychotic problems are actually *caused* by dopamine dysfunction, blocking D2 receptors will calm people (and animals) down, often without too much sedation. If too much is given, then you start getting twitches and such...
Anyway, since the days of Thorazine and the other phenothiazines (which include perphenazine, btw), researches have looked for drugs that block D2 receptors in treating psychotic states. Because the drugs are basically tranquilizers--give anybody an antipsychotic and they'll calm down--tests in animals look for key effects that indicate dopamine blockade.
As for why you'd want to block off those dopamine receptors...well...a lot of people don't. That's why there are long acting injections of AP/AAP drugs that can be given by court order. The older drugs, in particular, could cause severe depression ("neuroleptic induced dysphoria").The newer drugs, and moderate doses of some older ones, aren't so bad. I take 30mgs/Abilify. That's roughly equal to 400mgs/Thorazine. But if I took 400mgs/Thorazine, I'd probably be twitching and depressed. So, the newer drugs get the job done, but they're more tolerable.
Some people with depression need what a neuroleptic offers--a bit of apathy, distance between themselves and their emotional processes--either alone or in a cocktail. Back in the day, there were combo pills with 1 part amphetamine and 1 part neuroleptic. ThoraDex, StelaDex (stelazine and dexedrine), Eskatrol, etc. Sounds odd today, but these drugs functioned a lot like modern AD, but they worked faster and could be euphoric. One drug combined Stelazine and Parnate in a fixed ration.
So...yeah...neuroleptics/major tranquilizers are odd drugs. Some people need them (I'm raising my hand right now), and even those who don't have bipolar I or schizophrenia can benefit from using them, at least for a while. The modern ones are more tolerable. Higher doses can spell trouble for anybody, but especially people with mood disorders.
Hope this helps!
poster:Christ_empowered
thread:1089116
URL: http://www.dr-bob.org/babble/20160501/msgs/1089127.html