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List of cocaine analogues: Wikis

  

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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 benzoyloxytropanes.

Contents

Analogues with both stimulant & local anesthetic effects.

See some of Clarke's contributions

Quinuclidine Analogues

Phenyltropanes

See: List of Phenyltropanes

Piperidine Analogues

GBR Analogs

Benztropine Analogs

  • Benztropine
  • Difluoropine (more selective as a DARI than cocaine. Also an anticholinergic & antihistamine)
  • AHN 1-055 Same structure as for benztropine but 4',4'-bisfluorinated.
  • GA 103 N-phenylpropyl bis-4-fluorobenztropine
  • JHW 007[2] N-(n-butyl)-3α-[bis(4'-fluorophenyl)methoxy]-tropane

"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.[3][4]

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.[3]

This is remarkable considering unmodified (native) benztropine is 60 times more active as an anticholinergic than as a dopaminergic.[3]

M1 receptor considerations aside, these analogs stil wont substitute for cocaine, and have no propensity to elevate locomotor activity.

Local anesthetics (not usually CNS stimulants)

Note: Certain of the local anesthetics still have residual DRI properties,[5] 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.[5]

Analogues for other purposes

See also

References

  1. ^ Gatley SJ, Yu DW, Fowler JS, MacGregor RR, Schlyer DJ, Dewey SL, Wolf AP, Martin T, Shea CE, Volkow ND (March 1994). "Studies with differentially labeled [11C]cocaine, [11C]norcocaine, [11C]benzoylecgonine, and [11C]- and 4'-[18F]fluorococaine to probe the extent to which [11C]cocaine metabolites contribute to PET images of the baboon brain". Journal of Neurochemistry 62 (3): 1154–62. PMID 8113802.  
  2. ^ Tanda G, Newman A, Ebbs AL, Tronci V, Green J, Tallarida RJ, Katz JL.Combinations of Cocaine with other Dopamine Uptake Inhibitors: Assessment of Additivity. J Pharmacol Exp Ther. 2009 May 29. PMID 19483071
  3. ^ a b c 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
  4. ^ Runyon SP, Carroll FI. Dopamine transporter ligands: recent developments and therapeutic potential. Curr Top Med Chem. 2006;6(17):1825-43. PMID 17017960
  5. ^ a b 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

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