<pyridinyl_30>
Bluelighter
- Joined
- Dec 20, 2007
- Messages
- 404
Electronegativity is a useful concept when considered alongside with atomic size in both organic chemistry and pharmacology.
F is the most electronegative (electron withdrawing) halogen, but it is only about the size of a H atom. All attached halogens have three pairs of lone pairs of electrons. F is basically useless by itself; for example, 4-FA is only about a 1/3rd as good as regular amphetamine. Next, is Cl; Cl is you best bet as far as the halogens go. Take a perusal of the Physician's Desk Reference and you will find Cl aplenty represented in psychoactive drug structures. Br is heavier than Cl and is too toxic; bromazepam, for instance, is the one of the few benzodiazepines that causes liver damage. I is the largest/heaviest and most electropositive halogen, but it makes for weak psychedelics.
3,4-dichloroamphetamine has shown the most potential in animals studies as far as level of self-administering, a measure of addiction potential. Addiction potential is related to the dopamine neurotransmitter system. I would suggest
3,4-dichlormethcathinone perhaps. I say 3,4-dichloro over plain 4-chloro because the former is a closer analogue to dopamine. Reinforcing dopamine is the whole point of addictive drug design. An aromatic Cl functional group is somewhat similar to a hydroxy but crosses the blood brain barrier a lot better. Cl is basically
non-toxic.
F is the most electronegative (electron withdrawing) halogen, but it is only about the size of a H atom. All attached halogens have three pairs of lone pairs of electrons. F is basically useless by itself; for example, 4-FA is only about a 1/3rd as good as regular amphetamine. Next, is Cl; Cl is you best bet as far as the halogens go. Take a perusal of the Physician's Desk Reference and you will find Cl aplenty represented in psychoactive drug structures. Br is heavier than Cl and is too toxic; bromazepam, for instance, is the one of the few benzodiazepines that causes liver damage. I is the largest/heaviest and most electropositive halogen, but it makes for weak psychedelics.
3,4-dichloroamphetamine has shown the most potential in animals studies as far as level of self-administering, a measure of addiction potential. Addiction potential is related to the dopamine neurotransmitter system. I would suggest
3,4-dichlormethcathinone perhaps. I say 3,4-dichloro over plain 4-chloro because the former is a closer analogue to dopamine. Reinforcing dopamine is the whole point of addictive drug design. An aromatic Cl functional group is somewhat similar to a hydroxy but crosses the blood brain barrier a lot better. Cl is basically
non-toxic.
(it's not a question, I don't want an answer)
