# Substituted piperazine

Substituted piperazines are a class of chemical compounds based on a piperazine core. Some are used as recreational drugs and some are used in scientific research.

## List of substituted piperazines
### Benzylpiperazines

* 1-Benzylpiperazine (BZP)
* 1-Methyl-4-benzylpiperazine (MBZP)
* 1,4-Dibenzylpiperazine (DBZP)
* 3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
* 4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
* Methoxypiperamide (MeOP, MEXP) ((4-methoxyphenyl)(4-methylpiperazin-1-yl)methanone)
* Sunifiram (1-benzoyl-4-propanoylpiperazine)
* 3-Methylbenzylpiperazine (3-MeBZP)
* Befuraline (also produces benzylpiperazine as a metabolite)
* Fipexide (also produces substituted benzylpiperazine as a metabolite)
* Piberaline (also produces benzylpiperazine as a metabolite)

### Phenylpiperazines
#### ortho-Substituted

* 2-Chlorophenylpiperazine (oCPP)
* 2-Methylphenylpiperazine (oMPP)
* 2-Methoxyphenylpiperazine (oMeOPP)
* Vortioxetine
Enpiprazole is known to produce oCPP as a metabolite.
Enciprazine was initially anticipated to produce oMeOPP as a metabolite, but this turned out not to be the case.

#### meta-Substituted

* 3-Chlorophenylpiperazine (mCPP)
* 3-Methoxyphenylpiperazine (mMeOPP)
* 3-Trifluoromethylphenylpiperazine (TFMPP)
* 1-(3-Chlorophenyl)-4-(2-phenylethyl)piperazine (3C-PEP)
Trazodone, nefazodone, etoperidone, mepiprazole, and others produce mCPP as a metabolite.

#### para-Substituted

* 4-Chlorophenylpiperazine (pCPP)
* 4-Fluorophenylpiperazine (pFPP)
* 4-Methylphenylpiperazine (pMPP)
* 4-Methoxyphenylpiperazine (pMeOPP, MeOPP)
* 4-Nitrophenylpiperazine (pNPP; PAL-175) – selective partial serotonin releasing agent
* 4-Trifluoromethylphenylpiperazine (pTFMPP)

#### Multiple substitutions

* 2,3-Dichlorophenylpiperazine (2,3-DCPP)
* 3,4-Dichlorophenylpiperazine (3,4-DCPP)
* 2,3-Dimethylphenylpiperazine (DMPP)
* 3-Trifluoromethyl-4-chlorophenylpiperazine (TFMCPP; PAL-179) – selective partial serotonin releasing agent

#### Others

* 1-Phenylpiperazine (PP)

### Other arylpiperazines

* 1-(1-Naphthyl)piperazine (1-NP)
* 1-(2-Pyrimidinyl)piperazine (1-PP)
* ORG-12962 (1-(5-trifluoromethyl-6-chloropyridin-2-yl)piperazine)
* Quipazine (2-piperazin-1-ylquinoline)
Many azapirones such as buspirone, gepirone, and tandospirone produce 1-PP as a metabolite.

### By drug class

Antianginals
* Ranolazine
* Trimetazidine
Antidepressants
* Amoxapine
* Befuraline
* Buspirone
* Flesinoxan
* Gepirone
* Ipsapirone
* Nefazodone
* Piberaline
* Tandospirone
* Trazodone
* Vilazodone
* Vortioxetine
* Zalospirone
Antihistamines
* Buclizine
* Cetirizine
* Cinnarizine
* Cyclizine
* Hydroxyzine
* Levocetirizine
* Meclizine
* Niaprazine
Antiserotonergics
* EGIS-7625
Antipsychotics
* Typical
** Flupentixol
** Fluphenazine
** Perphenazine
** Prochlorperazine
** Thiothixene
** Trifluoperazine
** Zuclopenthixol
** Acetophenazine
** Carfenazine
* Atypical
** Amperozide
** Aripiprazole
** Clozapine
** Lurasidone
** Olanzapine
** Perospirone
** Ziprasidone
** Quetiapine
** Cariprazine
Recreational Drugs
* 4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
* 1-Benzylpiperazine (BZP)
* 2,3-Dichlorophenylpiperazine (DCPP)
* 1,4-Dibenzylpiperazine (DBZP)
* 4-Methyl-1-benzylpiperazine (MBZP)
* 3-Chlorophenylpiperazine (mCPP)
* 3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
* 4-Methoxyphenylpiperazine (MeOPP)
* Methoxypiperamide (MeOP or MEXP)
* 4-Chlorophenylpiperazine (pCPP)
* 4-Fluorophenylpiperazine (pFPP)
* 3-Trifluoromethylphenylpiperazine (TFMPP)
Urologicals
* Sildenafil
* Vardenafil
Others
* 6-Nitroquipazine
* Antrafenine
* Diethylcarbamazine
* Diphenazine
* Fipexide
* Imatinib
* NSI-189
* Pipobroman (antineoplastic agent)
* Quipazine
* Sunifiram (nootropic)
* Tolpiprazole (tranquilizer)

## Activities

Monoamine release (EC$_{50}$Tooltip half-maximal effective concentration, nM) of arylpiperazines :
| Compound | PAL # | Serotonin | Norepinephrine | Dopamine | Type | Ref |
| 1-Benzylpiperazine (BZP) | ND | 6050–>100000 | 62.2–68 | 175–600 | NDRA | |
| 1-Phenylpiperazine (PP) | ND | 880 | 186 | 2530 | SNRA | |
| 2-Me-PP (oMPP) | PAL-169 | 175 | 39.1 | 296–542 | SNDRA | |
| 2-OMe-PP (oMeOPP) | ND | ND | ND | ND | ND | ND |
| 2-TFM-PP (oTFMPP) | ND | 570 | 350 | 11200 | SNRA | |
| 2-SMe-PP (oMTPP) | ND | 270 | >10000 | >10000 | SRA | |
| 2-Et-PP (oEtPP) | ND | 290 | 830 | >10000 | SNRA | |
| 2-Chloro-PP (oCPP) | ND | 310 | 26 | >3000 | NRA | |
| 2-Bromo-PP (oBPP) | ND | 132 | 33 | 250 | SNDRA | |
| 2-Nitro-PP (oNPP) | ND | 1870 | 770 | >10000 | SNRA | |
| 3-Chloro-PP (mCPP) | ND | 28–39 | 1400–>10000 | >10000–63000 | SRA | |
| 3-Fluoro-PP (mFPP) | ND | 115 | 340 | 2400 | SNRA | |
| 3-Me-PP (mMPP) | ND | 110 | >20000 | >20000 | SRA | |
| 3-OMe-PP (mMeOPP) | ND | 650 | >10000 | >10000 | SRA | |
| 3-OH-PP (mOHPP) | ND | 230 | 174 | 2500 | SNRA | |
| 3-TFM-PP (TFMPP) | ND | 121 | >10000 | >10000 | SRA | |
| 4-Chloro-PP (pCPP) | ND | ND | ND | ND | ND | ND |
| 4-Fluoro-PP (pFPP) | ND | 230 | 3200 | >10000 | SRA | |
| 4-Me-PP (pMPP) | PAL-233 | 220 | >10000 | >20000 | SRA | |
| 4-OMe-PP (pMeOPP) | ND | 3200 | 440–1500 | 6300–11000 | SNDRA | |
| 4-TFM-PP (pTFMPP) | ND | ND | ND | ND | ND | ND |
| 4-Ac-PP (pAcPP) | ND | 50 | 150 | 3000 | SNRA | |
| 4-CN-PP (pCNPP) | ND | 36 | 6300 | >10000 | SRA | |
| 4-Phenyl-PP (pPhPP) | ND | >10000 | 1520 | 5200 | NDRA | |
| 4-OH-PP (pOHPP) | ND | >10000 | 230 | 850 | NDRA | |
| 4-Nitro-PP (pNPP) | PAL-175 | 19–43 | >10000 | >10000 | SRA | |
| 2,3-Dichloro-PP (2,3-DCPP) | ND | 10 | 36 | 108 | SNDRA | |
| 2,3-DiMe-PP (2,3-DMPP) | PAL-218 | 24–26 | 13.7–56 | 1207–1320 | SNRA | |
| 2,4-Difluoro-PP (2,4-DFPP) | ND | 470 | 2300 | >10000 | SNRA | |
| 3,4-Dichloro-PP (3,4-DCPP) | ND | ND | ND | ND | ND | ND |
| 3,4-Difluoro-PP (3,4-DFPP) | ND | 76 | 9200 | >10000 | SRA | |
| 3-TFM-4-Cl-PP (TFMCPP) | PAL-179 | 33 | >10000 | >10000 | SRA | |
| Notes: Assays were done using rat brain synaptosomes. |||||||