From Wikipedia, the free encyclopedia
This is a list of cocaine
analogues. A cocaine
analogue is a drug manufactured from cocaine or has its
basis as a total
synthesis of cocaine, but is modified to alter its effect.
These include both intracellular sodium channel blocker anesthetics
and phenyltropane stimulant dopamine reuptake inhibitor
ligands & certain piperidines. Many of the
stimulant created analogues are of a class of C-2 substituted
See some of Clarke's
See: List of Phenyltropanes
(more selective as a DARI than cocaine. Also an anticholinergic
- AHN 1-055 Same structure as for benztropine but
- GA 103 N-phenylpropyl bis-4-fluorobenztropine
- JHW 007
"Difluoropine" is not a phenyltropane but actually belongs to
the benztropine family of DRIs.
In certain respects these are important because they share SAR
overlap with GBR 12909
and related analogs.
SARs have shown that 4',4'-difluorination is an excellent way to
boost DAT activity of benztropine, and gives excellent selectivity
over the SERT and the NET.
Furthermore, replacing the N-Me with, e.g. n-phenylpropyl helps
to bring muscarinic activity down to something that
is the same as DRI affinty.
This is remarkable considering unmodified (native) benztropine
is 60 times more active as an anticholinergic than as a
M1 receptor considerations aside, these analogs stil wont
substitute for cocaine, and have no propensity to elevate locomotor
anesthetics (not usually CNS stimulants)
Note: Certain of the local anesthetics still have residual DRI
although not normally ones that are easily available. These are
expected to be more cardiotoxic than phenyltropanes. For example,
dimethocaine has behavioral stimulant effects (and therefore not
here listed below) if a dose of it is taken that is 10 times the
amount of cocaine. Dimethocaine is equipotent to cocaine in terms
of its anesthetic equivalency.
Analogues for other
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4'-[18F]fluorococaine to probe the extent to which [11C]cocaine
metabolites contribute to PET images of the baboon brain".
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- ^ a
Rothman RB, Baumann MH, Prisinzano TE, Newman AH. Dopamine
transport inhibitors based on GBR12909 and benztropine as potential
medications to treat cocaine addiction. Biochem Pharmacol. 2008 Jan
1;75(1):2-16. PMID 17897630
- ^ Runyon SP, Carroll FI.
Dopamine transporter ligands: recent developments and therapeutic
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Wilcox, K.M., Kimmel, H.L., Lindsey, K.P., Votaw, J.R., Goodman,
M.M., Howell, L.L. In vivo comparison of the reinforcing and
dopamine transporter effects of local anesthetics in rhesus
monkeys. Synapse, 58: 220-228, 2005. PDF