From: lamontg@carson.u.washington.edu (Lamont Granquist)
Subject: Re: Neurotransmitter questions
Organization: 'Operation: Mindcrime'
Date: Fri, 9 Oct 1992 08:57:25 GMT

alves@calvin.usc.edu (William Alves) writes:
>I am merely an interested amateur who as been reading a few books, but
>they have left me with a few questions, and I hope that some of you will
>indulge me by posting answers to a couple of them. Perhaps the answers
>aren't known, but the things I have read so far have not made that clear.
>
>First, this whole neurotransmitter business. As I see it, there are only
>two possible effects a neurotransmitter can have on a neuron - it can
>inhibit or excite the cell. Then doesn't it seem logical that there would
>be only two types of neurotransmitters, instead of the pharmacopeia that
>has been discovered? What is the difference between inhibition from one
>neurotransmitter and another?

Well, in a nutshell, your body is more complex than that.  Like what would
happen if your body dumped some adrenalin into your system and every nerve
in your body responded to it? -- thats probably the simplest thing to consider.

>Second, the non-technical sources I have read have made a big deal out of
>the chemical similarities between certain hallucinogens (LSD for example)
>and certain neurotransmitters (serotonin for example). Yet is simple 
>mimickry behind all of the drug's effects? If that is so, why do different
>serotonin-like drugs have wildly different effects, and others have none
>at all?

Cuz, for example, you can mimic 5-HT at 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2A
and 5-HT2B (*) receptor sites in addition to "mimicing 5-HT" via blocking the
reuptake 5-HT at the reuptake transporter.  Oh, and you can also enter the
neuron and release a neurotransmitter directly like amphetamines do to DA.
And then there is also potential effects to second messangers and effects on
calcium channels and probably other shit that I'm forgetting or haven't yet
learned about.. (oh and then there's chronic effects like the receptor 
down/up regulation which is thought to be responsible for antidepressant
responce and also things like heroin resonance -- but this might be due to
more complicated factors like second messagers or axonal arborization -- 
blah, blah, blah...) 

Oh yeah, and the number one important thing about a psychoactive drug is that
its got to cross the Blood-Brain Barrier.  Its quite possible that you might
have a "drug" that is active via cerebrospinal injection, but isn't at all
via any other route.  This is the case with prodrugs, (sorta) where what
happens is that a chemical crosses the BBB and then is metabolized into the
active drug.

(*) not quite sure if I've listed all the 5-HT receptors correctly here...
    its 2am man, cut me some slack, you get the idea...

>I hope I don't get deluged with "go to the library"-type flames. It's true
>I haven't gone to med school, but I have been to the library, and that's
>what has left me with these questions. Thanks very much for any help.

"Drugs and the Brain" by Solomon Snyder.  Scientific American Publications.

-- 
Lamont Granquist  lamontg@u.washington.edu
  "'Tis an ill wind that blows no minds."
                                      -- Principia Discordia
Newsgroups: bionet.neuroscience