This is a list of methylphenidate (MPH or MPD) analogues, or Phenidates. The most well known compound from this family, methylphenidate, is widely prescribed around the world for the treatment of attention deficit hyperactivity disorder (ADHD) and certain other indications. Several other derivatives including rimiterol, phacetoperane and pipradrol also have more limited medical application. A rather larger number of these compounds have been sold in recent years as designer drugs, either as quasi-legal substitutes for illicit stimulants such as methamphetamine or cocaine, or as purported "study drugs" or nootropics.[1][2][3]
More structurally diverse compounds such as desoxypipradrol (and thus pipradrol, including such derivatives as AL-1095, diphemethoxidine, SCH-5472 and D2PM), and even mefloquine, 2-benzylpiperidine, rimiterol, enpiroline and DMBMPP, can also be considered structurally related, with the former ones also functionally so, as loosely analogous compounds. The acyl group has sometimes been replaced with similar length ketones to increase duration. Alternatively, the methoxycarbonyl has in some cases been replaced with an alkyl group.[4][5]
Dozens more phenidates and related compounds are known from the academic and patent literature, and molecular modelling and receptor binding studies have established that the aryl and acyl substituents in the phenidate series are functionally identical to the aryl and acyl groups in the phenyltropane series of drugs, suggesting that the central core of these molecules is primarily acting merely as a scaffold to correctly orientate the binding groups, and for each of the hundreds of phenyltropanes that are known, there may be a phenidate equivalent with a comparable activity profile. Albeit with the respective difference in their entropy of binding: cocaine being −5.6 kcal/mol and methylphenidate being −25.5 kcal/mol (Δs°, measured using [3H]GBR 1278 @ 25 °C).[a]
Notable phenidate derivatives
General structure of phenidate derivatives, where R is nearly always hydrogen but can be alkyl, R1 is usually phenyl or substituted phenyl but rarely other aryl groups, R2 is usually acyl but can be alkyl or other substitutions, and Cyc is nearly always piperidine but rarely other heterocycles
Alternate two dimensional rendering of "D-threo-methylphenidate"; demonstrating the plasticity of the piperidine ring in a 'flexed' or "chair" conformation. (the latter term can denote a structure containing a bridge in the ring when so-named, unlike the above).
N.B. although the cyclohexane conformation, if considering both the hydrogen on the plain bond and the implicit carbon on the dotted bond are not shown as positioned as would be for the least energy state inherent to what rules apply, internally, to the molecule in and of itself: possibility of movement between putative other ligand sites in suchwise, here regarding what circumstance allows for describing it as "flexed" thus mean it has shown tendency for change in situ depending on its environment and adjacent sites of potential interaction as against its least energy state.
Methylphenidate (and its derivatives) have two chiral centers, meaning that it, and each of its analogues, have four possible enantiomers, each with differing pharmacokinetics and receptor binding profiles. In practice methylphenidate is most commonly used as pairs of diastereomers rather than isolated single enantiomers or a mixture of all four isomers. Forms include the racemate, the enantiopure (dextro or levo) of its stereoisomers; erythro or threo (either + or -) among its diastereoisomers, the chiral isomers S,S; S,R/R,S or R,R and, lastly, the isomeric conformers (which are not absolute) of either its anti- or gauche- rotamer. The variant with optimized efficacy is not the usually attested generic or common pharmaceutical brands (e.g. Ritalin, Daytrana etc.) but the (R,R)-dextro-(+)-threo-anti (sold as Focalin), which has a binding profile on par with or better than that of cocaine.[b] (Note however the measure of fivefold (5×) discrepancy in the entropy of binding at their presumed shared target binding site, which may account for the higher abuse potential of cocaine over methylphenidate despite affinity for associating; i.e the latter dissociates more readily once bound despite efficacy for binding.[c]) Furthermore, the energy to change between its two rotamers involves the stabilizing of the hydrogen bond between the protonated amine (of an 8.5 pKa) with the ester carbonyl resulting in reduced instances of "gauche—gauche" interactions via its favoring for activity the "anti"-conformer for putative homergic-psychostimulating pharmacokinetic properties, postulating that one inherent conformational isomer ("anti") is necessitated for the activity of the threo diastereoisomer.[d]
Also of note is that methylphenidate in demethylated form is acidic; a metabolite (and precursor) known as ritalinic acid.[8] This gives the potential to yield a conjugatesalt[9] form effectively protonated by a salt nearly chemically duplicate/identical to its own structure; creating a "methylphenidate ritalinate".[10]
Receptor binding profiles of selected methylphenidate analogues
Both analogues 374 & 375 displayed higher potency than methylphenidate at DAT. In further comparison, 375 (the 2-naphthyl) was additionally two & a half times more potent than 374 (the 1-naphthyl isomer).[f]
Structures of Azido-iodo-N-benzyl analogues of methylphenidate with affinities.[13]
Azido-iodo-N-benzyl methylphenidate analogs inhibitition of [3H]WIN 35428 binding and [3H]dopamine uptake at hDAT N2A neuroblastoma cells.[13] (Each Ki or IC50 value represents data from at least three independent experiments with each data point on the curve performed in duplicate)
Structure
Compound
R1
R2
Ki (nM) (Inhibition of [3H]WIN 35428 binding)
IC50 (nM) (Inhibition of [3H]DA uptake)
(±)—threo-methylphenidate
H
H
25 ± 1
156 ± 58
(±)—4-I-methylphenidate
para-iodo
H
14 ± 3ɑ
11 ± 2b
(±)—3-I-methylphenidate
meta-iodo
H
4.5 ± 1ɑ
14 ± 5b
(±)—p-N3-N-Bn-4-I-methylphenidate
para-iodo
para-N3-N-Benzyl
363 ± 28ɑ
2764 ± 196bc
(±)—m-N3-N-Bn-4-I-methylphenidate
para-iodo
meta-N3-N-Benzyl
2754 ± 169ɑ
7966 ± 348bc
(±)—o-N3-N-Bn-4-I-methylphenidate
para-iodo
ortho-N3-N-Benzyl
517 ± 65ɑ
1232 ± 70bc
(±)—p-N3-N-Bn-3-I-methylphenidate
meta-iodo
para-N3-N-Benzyl
658 ± 70ɑ
1828 ± 261bc
(±)—m-N3-N-Bn-3-I-methylphenidate
meta-iodo
meta-N3-N-Benzyl
2056 ± 73ɑ
4627 ± 238bc
(±)—o-N3-N-Bn-3-I-methylphenidate
meta-iodo
ortho-N3-N-Benzyl
1112 ± 163ɑ
2696 ± 178bc
(±)—N-Bn-methylphenidate
H
N-Benzyl
—
—
(±)—N-Bn-3-chloro-methylphenidate
3-Cl
N-Benzyl
—
—
(±)—N-Bn-3,4-dichloro-methylphenidate
3,4-diCl
N-Benzyl
—
—
(±)—p-chloro-N-Bn-methylphenidate
H
para-Cl-N-Benzyl
—
—
(±)—p-methoxy-N-Bn-methylphenidate
H
para-OMe-N-Benzyl
—
—
(±)—m-chloro-N-Bn-methylphenidate
H
meta-Cl-N-Benzyl
—
—
(±)—p-nitro-N-Bn-methylphenidate
H
para-NO2-N-Benzyl
—
—
ɑp <0.05 versus Ki of (±)—threo-methylphenidate.
bp <0.05 versus IC50 of (±)—threo-methylphenidate.
Alkyl RR/SS diastereomer analogs of methylphenidate[4] (RS/SR diastereomer values of otherwise same compounds given in small grey typeface[4])
Structure
R1
R2
R3
Dopamine transporter Ki (nM) (Inhibition of [I125H]RTI-55 binding)
DA uptake IC50 (nM)
Serotonin transporter Ki (nM) (Inhibition of [I125H]RTI-55 binding)
5HT uptake IC50 (nM)
Norepinephrine transporter Ki (nM) (Inhibition of [I125H]RTI-55 binding)
NE uptake IC50 (nM)
NE/DA selectivity (binding displacement)
NE/DA selectivity (uptake blocking)
Cocaine
— ɑ
— b
— c
500 ± 65
240 ± 15
340 ± 40
250 ± 40
500 ± 90
210 ± 30
1.0
0.88
H
COOCH3
H
110 ± 9
79 ± 16
65,000 ± 4,000
5,100 ± 7,000
660 ± 50
61 ± 14
6.0
0.77
4-chloro
COOCH3
H
25 ± 8 2,000 ± 600
11 ± 28 2,700 ± 1,000
6,000 ± 100 5,900 ± 200
>9,800 >10 mM
110 ± 40 >6,100
11 ± 3 1,400 ± 400
4.4
1.0
4-chloro
methyl
H
180 ± 70 >3,900
22 ± 7 1,500 ± 700
4,900 ± 500 >9,100
1,900 ± 300 4,700 ± 800
360 ± 140 >6,300
35 ± 13 3,200 ± 800
2.0
1.6
4-chloro
ethyl
H
37 ± 10 1,800 ± 300
23 ± 5 2,800 ± 700
7,800 ± 800 4,200 ± 400
2,400 ± 400 4,100 ± 1,000
360 ± 60 >9,200
210 ± 30 1,300 ± 400
9.7
9.1
4-chloro
propyl
H
11 ± 3 380 ± 40
7.4 ± 0.4 450 ± 60
2,700 ± 600 3,200 ± 1,100
2,900 ± 1,100 1,300 ± 7
200 ± 80 1,400 ± 400
50 ± 15 200 ± 50
18.0
6.8
4-chloro
isopropyl
H
46 ± 16 900 ± 320
32 ± 6 990 ± 280
5,300 ± 1,300 >10 mM
3,300 ± 400 —
810 ± 170 >10 mM
51 ± 20 —
18.0
1.6
4-chloro
butyl
H
7.8 ± 1.1 290 ± 70
8.2 ± 2.1 170 ± 40
4,300 ± 400 4,800 ± 700
4,000 ± 400 3,300 ± 600
230 ± 30 1,600 ± 300
26 ± 7 180 ± 60
29.0
3.2
4-chloro
isobutyl
H
16 ± 4 170 ± 50
8.6 ± 2.9 380 ± 130
5,900 ± 900 4,300 ± 500
490 ± 80 540 ± 150
840 ± 130 4,500 ± 1,500
120 ± 40 750 ± 170
53.0
14.0
4-chloro
pentyl
H
23 ± 7 870 ± 140
45 ± 14 650 ± 20
2,200 ± 100 3,600 ± 1,000
1,500 ± 300 1,700 ± 700
160 ± 40 1,500 ± 300
49 ± 16 860 ± 330
7.0
1.1
4-chloro
isopentyl
H
3.6 ± 1.2 510 ± 170
14 ± 2 680 ± 120
5,000 ± 470 6,700 ± 500
7,300 ± 1,400 >8,300
830 ± 110 12,000 ± 1,400
210 ± 40 3,000 ± 540
230.0
15.0
4-chloro
neopentyl
H
120 ± 40 600 ± 40
60 ± 2 670 ± 260
3,900 ± 500 3,500 ± 1,000
>8,300 1,800 ± 600
1,400 ± 400 >5,500
520 ± 110 730 ± 250
12.0
8.7
4-chloro
cyclopentylmethyl
H
9.4 ± 1.5 310 ± 80
21 ± 1 180 ± 20
2,900 ± 80 3,200 ± 700
2,100 ± 900 5,600 ± 1,400
1,700 ± 600 2,600 ± 800
310 ± 40 730 ± 230
180.0
15.0
4-chloro
cyclohexylmethyl
H
130 ± 40 260 ± 30
230 ± 70 410 ± 60
900 ± 400 3,700 ± 500
1,000 ± 200 6,400 ± 1,300
4,200 ± 200 4,300 ± 200
940 ± 140 1,700 ± 600
32.0
4.1
4-chloro
benzyl
H
440 ± 110 550 ± 60
370 ± 90 390 ± 60
1,100 ± 200 4,300 ± 800
1,100 ± 200 4,700 ± 500
2,900 ± 800 4,000 ± 800
2,900 ± 600 >8,800
6.6
7.8
4-chloro
phenethyl
H
24 ± 9 700 ± 90
160 ± 20 420 ± 140
640 ± 60 1,800 ± 70
650 ± 210 210 ± 900d
1,800 ± 600 2,400 ± 700
680 ± 240 610 ± 150
75.0
4.3
4-chloro
phenpropyl
H
440 ± 150 2,900 ± 900
290 ± 90 1,400 ± 400
700 ± 200 1,500 ± 200
1,600 ± 300 1,200 ± 400
490 ± 100 1,500 ± 200
600 ± 140 1,700 ± 200
1.1
2.1
4-chloro
3-pentyl
H
400 ± 80 >5,700
240 ± 60 1,200 ± 90
3,900 ± 300 4,800 ± 1,100
>9,400 >9,600
970 ± 290 4,300 ± 200
330 ± 80 3,800 ± 30
2.4
1.4
4-chloro
cyclopentyl
H
36 ± 10 690 ± 140
27 ± 8.3 240 ± 30
5,700 ± 1,100 4,600 ± 700
4,600 ± 800 4,200 ± 900
380 ± 120 3,300 ± 800
44 ± 18 1,000 ± 300
11.0
1.6
3-chloro
isobutyl
H
3.7 ± 1.1 140 ± 30
2.8 ± 0.4 88 ± 12
3,200 ± 400 3,200 ± 400
2,100 ± 100 870 ± 230
23 ± 6 340 ± 50
14 ± 1 73 ± 5
6.2
5.0
3,4-dichloro
COOCH3
H
1.4 ± 0.1 90 ± 14
23 ± 3 800 ± 110
1,600 ± 150 2,500 ± 420
540 ± 110 1,100 ± 90
14 ± 6 4,200 ± 1,900
10 ± 1 190 ± 50
10.0
0.43
3,4-dichloro
propyl
H
0.97 ± 0.31 43 ± 9
4.5 ± 0.4 88 ± 32
1,800 ± 500 450 ± 80
560 ± 120 180 ± 60
3.9 ± 1.4 30 ± 8
8.1 ± 3.8 47 ± 22
4.0
1.8
3,4-dichloro
butyl
H
2.3 ± 0.2 29 ± 5
5.7 ± 0.5 67 ± 13
1,300 ± 300 1,100 ± 200
1,400 ± 300 550 ± 80
12 ± 3 31 ± 11
27 ± 10 63 ± 27
5.2
4.7
3,4-dichloro
isobutyl
H
1.0 ± 0.5 31 ± 11
5.5 ± 1.3 13 ± 3
1,600 ± 100 450 ± 40
1,100 ± 300 290 ± 60
25 ± 9 120 ± 30
9.0 ± 1.2 19 ± 3
25.0
1.6
3,4-dichloro
isobutyl
CH3
6.6 ± 0.9 44 ± 12
13 ± 4 45 ± 4
1,300 ± 200 1,500 ± 300
1,400 ± 500 2,400 ± 700
190 ± 60 660 ± 130
28 ± 3 100 ± 19
29.0
2.2
4-methoxy
isobutyl
H
52 ± 16 770 ± 220
25 ± 9 400 ± 120
2,800 ± 600 950 ± 190
3,500 ± 500 1,200 ± 300
3,100 ± 200 16,000 ± 2,000
410 ± 90 1,600 ± 400
60.0
16.0
3-methoxy
isobutyl
H
22 ± 5 950 ± 190
35 ± 12 140 ± 20
4,200 ± 400 3,800 ± 600
2,700 ± 800 2,600 ± 300
3,800 ± 500 12,000 ± 2,300
330 ± 40 1,400 ± 90
170.0
9.4
4-isopropyl
isobutyl
H
3,300 ± 600 >6,500
4,000 ± 400 >9,100
3,300 ± 600 1,700 ± 500
4,700 ± 700 1,700 ± 100
2,500 ± 600 3,200 ± 600
7,100 ± 1,800 >8,700
0.76
1.8
H
COCH3
H
370 ± 70
190 ± 50
7,800 ± 1,200
>9,700
2,700 ± 400
220 ± 30
7.3
1.2
ɑ H = Equivalent overlay of structure sharing functional group
b CO2CH3 (i.e. COOCH3) = Equivalent overlay of structure sharing functional group
c CH3 = Equivalent overlay of structure sharing functional group
d possible typographical error in original source; e.g. 2,100 ± 900 or 900 ± 210
Restricted rotational analogs of methylphenidate (quinolizidines)
Two of the compounds tested, the weakest two @ DAT & second to the final two on the table below, were designed to elucidate the necessity of both constrained rings in the efficacy of the below series of compounds at binding by removing one or the other of the two rings in their entirety. The first of the two retain the original piperidine ring had with methylphenidate but has the constrained B ring that is common to the restricted rotational analogues thereof removed. The one below lacks the piperdine ring native to methylphenidate but keeps the ring that hindered the flexibility of the original MPH conformation. Though their potency at binding is weak in comparison to the series, with the potency shared being approximately equal between the two; the latter compound (the one more nearly resembling the substrate class of dopaminergic releasing agents similar to phenmetrazine) is 8.3-fold more potent @ DA uptake.
Binding assaysg of rigid methylphenidate analogues[16]
Compoundɑ
R & X substitution(s)
Ki (nM) @ DAT with [33]WIN 35,065-2
nH @ DAT with [33]WIN 35,065-2
Ki (nM) or % inhibition @ NET with [33]Nisoxetine
nH @ NET with [33]Nisoxetine
Ki (nM) or % inhibition @ 5-HTT with [33]Citalopram
nH @ 5-HTT with [33]Citalopram
[33]DA uptake IC50 (nM)
Selectivity [33]Citalopram / [33]WIN 35,065-2
Selectivity [33]Nisoxetine / [33]WIN 35,065-2
Selectivity [33]Citalopram / [33]Nisoxetine
Cocaine
—
156 ± 11
1.03 ± 0.01
1,930 ± 360
0.82 ± 0.05
306 ± 13
1.12 ± 0.15
404 ± 26
2.0
12
0.16
Methylphenidate
—
74.6 ± 7.4
0.96 ± 0.08
270 ± 23
0.76 ± 0.06
14 ± 8%f
—
230 ± 16
>130
3.6
>47
3′,4′-dichloro-MPH
—
4.76 ± 0.62
2.07 ± 0.05
NDh
—
667 ± 83
1.07 ± 0.04
7.00 ± 140
140
—
—
—
6,610 ± 440
0.91 ± 0.01
11%b
—
3,550 ± 70
1.79 ± 0.55
8,490 ± 1,800
0.54
>0.76
<0.7
H
76.2 ± 3.4
1.05 ± 0.05
138 ± 9.0
1.12 ± 0.20
5,140 ± 670
1.29 ± 0.40
244 ± 2.5
67
1.8
37
3′,4′-diCl
3.39 ± 0.77
1.25 ± 0.29
28.4 ± 2.5
1.56 ± 0.80
121 ± 17
1.16 ± 0.31
11.0 ± 0.00
36
8.4
4.3
2′-Cl
480 ± 46
1.00 ± 0.09
2,750; 58%b
0.96
1,840 ± 70
1.18 ± 0.06
1,260 ± 290
3.8
5.7
0.67
—
34.6 ± 7.6
0.95 ± 0.18
160 ± 18
1.28 ± 0.12
102 ± 8.2
1.01 ± 0.02
87.6 ± 0.35
3.0
4.6
0.64
CH2OH
2,100 ± 697
0.87 ± 0.09
NDh
—
16.2 ± 0.05%f
—
10,400 ± 530
>4.8
—
—
CH3
7,610 ± 800
1.02 ± 0.03
8.3%b
—
11 ± 5%f
—
7,960 ± 290
>1.3
≫0.66
—
d R=OCH3, X=H
570 ± 49
0.94 ± 0.10
2,040; 64 ± 1.7%f
0.73
14 ± 3%f
—
1,850 ± 160
>18
3.6
>4.9
R=OH, X=H
6,250 ± 280
0.86 ± 0.03
23.7 ± 4.1%b
—
1 ± 1%f
—
10,700 ± 750
≫1.6
>0.80
—
R=OH, X=3′,4′-diCl
35.7 ± 3.2
1.00 ± 0.09
367 ± 42
1.74 ± 0.87
2,050 ± 110
1.15 ± 0.12
NDh
57
10
5.6
H
908 ± 160
0.88 ± 0.05
4030; 52%b
1.04
5 ± 1%f
—
12,400 ± 1,500
≫11
4.4
≫2.5
3′,4′-diCl
14.0 ± 1.2
1.27 ± 0.20
280 ± 76
0.68 ± 0.09
54 ± 2%f
—
NDh
~710
20
~36
R=OH, X=H
108 ± 7.0
0.89 ± 0.10
351 ± 85
0.94 ± 0.27
12 ± 2%f
—
680 ± 52
>93
3.3
>28
R=OH, X=3′,4′-diCl
2.46 ± 0.52
1.39 ± 0.20
27.9 ± 3.5
0.70 ± 0.01
168
1.02
NDh
68
11
6.0
R=OCH3, X=H
10.8 ± 0.8
0.97 ± 0.07
63.7 ± 2.8
0.84 ± 0.04
2,070; 73 ± 5%f
0.90
61.0 ± 9.3
190
5.9
32
R1=CH3, R2=H
178 ± 28
1.23 ± 0.09
694 ± 65
0.88 ± 0.13
427
1.39
368
2.4
3.9
0.62
R1=H, R2=CH3
119 ± 20
1.17 ± 0.12
76.0 ± 12
0.88 ± 0.06
243
1.17
248
2.0
0.64
3.2
—
175 ± 8.0
1.00 ± 0.04
1,520 ± 120
0.97 ± 0.06
19 ± 4%f
—
NDh
>57
8.69
>6.6
R=CH2CH3, X=H
27.6 ± 1.7
1.29 ± 0.05
441 ± 49
1.16 ± 0.19
2,390; 80%f
1.12
NDh
87
15
5.8
R=CH2CH3, X=3′,4′-diCl
3.44 ± 0.02
1.90 ± 0.05
102 ± 19
1.27 ± 0.10
286 ± 47
1.30 ± 0.10
NDh
83
30
2.8
R=CH2CH3, X=H
5.51 ± 0.93
1.15 ± 0.03
60.8 ± 9.6
0.75 ± 0.07
3,550; 86%f
0.95
NDh
640
11
58
R=CH2CH3, X=3′,4′-diCl
4.12 ± 0.95
1.57 ± 0.00
98.8 ± 8.7
1.07 ± 0.07
199 ± 17
1.24 ± 0.00
NDh
48
24
2.0
—
6,360 ± 1,300
1.00 ± 0.04
36 ± 10%c
—
22 ± 7%f
—
8,800 ± 870
>1.6
—
—
i —
4,560 ± 1,100
1.10 ± 0.09
534 ± 210c
0.96 ± 0.08
53 ± 6%f
—
1,060 ± 115
~2.2
0.12
~19
R1=CH2OH, R2=H, X=H
406 ± 4
1.07 ± 0.08
NDh
—
31.0 ± 1.5%f
—
1,520 ± 15
>25
—
—
R1=CH2OCH3, R2=H, X=H
89.9 ± 9.4
0.97 ± 0.04
NDh
—
47.8 ± 0.7%f
—
281 ± 19
~110
—
—
R1=CH2OH, R2=H, X=3′,4′-diCl
3.91 ± 0.49
1.21 ± 0.06
NDh
—
276; 94.6%f
0.89
22.5 ± 1.4
71
—
—
R1=H, R2=CO2CH3, X=3′,4′-diCl
363 ± 20
1.17 ± 0.41
NDh
—
2,570 ± 580
1.00 ± 00.1
317 ± 46
7.1
—
—
R1=CO2CH3, R2=H, X=2′-Cl
1,740 ± 200
0.98 ± 0.02
NDh
—
22.2 ± 2.5%f
—
2,660 ± 140
>5.7
—
—
ɑ Compounds tested as hydroclhoride (HCl) salts, unless otherwise noted.
b % inhibition caused by 5μM
c % inhibition caused by 10μM, as assayed by SRI
d Tested as free base
e Assayed by SRI (appropriate correction factor applied.)
f % inhibition of 10μM compound.
g Values expressed as x ± SEM of 2—5 replicate tests. (If no SEM shown, value is for an n of 1.)
Various MPH congener affinity values inclusive of norepinephrine & serotonin
Values for dl-threo-methylphenidate derivatives are the mean (s.d.)[17] of 3—6 determinations, or are the mean of duplicate determinations. Values of other compounds are the mean—s.d. for 3—4 determinations where indicated, or are results of single experiments which agree with the literature. All binding experiments were done in triplicate.[18]
ɑ Denotes that preparation of membrane and results extrapolated therefrom originated from frozen tissue, which is known to change results when interpreting against fresh tissue experiments.
p-hydroxymethylphenidate displays low brain penetrability, ascribed to its phenolic hydroxyl group undergoing ionization at physiological pH.
See also
HDMP-28 molecular model superimposed over β-CFT. cf.cocaine, and the phenyltropane class of drugs, including all subsets of related derivatives for either as pertaining in similarity to methylphenidate analogs.
Methylphenidate rendered in 3D (in blue) overlaid with 1-(2-Phenylethyl) piperazine skeleton (turquoise) showing the basic 3- point pharmacophore shared between them and other dopamine reuptake inhibitors such as 3C-PEP (which in turn is structurally related to the GBR stimulant compounds.)
References
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