CP-94253

Potent and selective serotonin 5-HT1B receptor agonist From Wikipedia, the free encyclopedia

CP-94253 is a drug of the tetrahydropyridinylpyrrolopyridine family which acts as a potent and selective serotonin 5-HT_1B receptor agonist, with approximately 25- and 40-fold selectivity over the closely related serotonin 5-HT_1D and 5-HT_1A receptors.^[1]

Other namesCP94253; CP-94,253

Drug classSerotonin 5-HT_1B receptor agonist

CAS Number

131084-35-0^Y

PubChem CID

4029677

Quick facts Clinical data, Other names ...

CP-94253
Clinical data

Other names	CP94253; CP-94,253
Drug class	Serotonin 5-HT_1B receptor agonist
Identifiers
IUPAC name 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine
CAS Number	131084-35-0^Y
PubChem CID	4029677
IUPHAR/BPS	3221
ChemSpider	3246572^N
UNII	FYC6YY5RYL
CompTox Dashboard (EPA)	DTXSID10470073
Chemical and physical data
Formula	C₁₅H₁₉N₃O
Molar mass	257.337 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES c13nc(OCCC)ccc1[nH]cc3C2=CCNCC2
InChI InChI=1S/C15H19N3O/c1-2-9-19-14-4-3-13-15(18-14)12(10-17-13)11-5-7-16-8-6-11/h3-5,10,16-17H,2,6-9H2,1H3^N Key:KWQWBZIGHIOKIO-UHFFFAOYSA-N^N
^NY (what is this?) (verify)

It has a range of behavioral effects, based on animal testing. The effects include the following: promoting wakefulness by increasing dopamine release in the brain;^[2]^[3] reducing food intake and promoting satiety;^[4]^[5]^[6] enhancing the reinforcing effects of cocaine;^[7]^[8]^[9]^[10] and possible antidepressant effects.^[11] In addition, CP-94253 reduces aggression without causing sedation in rodents.^[12]^[13]^[14]^[15]^[16]^[17]^[18]^[19]

A 2021 study^[20] found that "Regardless of sex, CP94253 decreased cocaine intake after abstinence and during resumption of SA [self-administration] and decreased cue reactivity" suggesting that agonism of the inhibitory 5-HT2B receptors may diminish the cognitive reward of cocaine usage and increased use of the drug without a period of abstinence may be a product of test subjects trying to achieve a previously rewarding experience through larger dosages of cocaine.

References

[1]
Koe KB, Nielsen JA, Macor JE, Heym J (1992). "Biochemical and behavioral studies of the 5-HT1B receptor agonist, CP-94,253". Drug Development Research. 26 (3): 241–250. doi:10.1002/ddr.430260305. S2CID 85358992.
[2]
Monti JM, Monti D, Jantos H, Ponzoni A (December 1995). "Effects of selective activation of the 5-HT1B receptor with CP-94,253 on sleep and wakefulness in the rat". Neuropharmacology. 34 (12): 1647–1651. doi:10.1016/0028-3908(95)00112-3. PMID 8788962. S2CID 11872727.
[3]
Iyer RN, Bradberry CW (April 1996). "Serotonin-mediated increase in prefrontal cortex dopamine release: pharmacological characterization". The Journal of Pharmacology and Experimental Therapeutics. 277 (1): 40–47. doi:10.1016/S0022-3565(25)12836-X. PMID 8613947.
[4]
Halford JC, Blundell JE (September 1996). "The 5-HT1B receptor agonist CP-94,253 reduces food intake and preserves the behavioural satiety sequence". Physiology & Behavior. 60 (3): 933–939. doi:10.1016/0031-9384(96)00073-x. PMID 8873272. S2CID 24349948.
[5]
Lee MD, Simansky KJ (June 1997). "CP-94, 253: a selective serotonin1B (5-HT1B) agonist that promotes satiety". Psychopharmacology. 131 (3): 264–270. doi:10.1007/s002130050292. PMID 9203237. S2CID 33969765.
[6]
Lee MD, Kennett GA, Dourish CT, Clifton PG (October 2002). "5-HT1B receptors modulate components of satiety in the rat: behavioural and pharmacological analyses of the selective serotonin1B agonist CP-94,253". Psychopharmacology. 164 (1): 49–60. doi:10.1007/s00213-002-1162-7. PMID 12373419. S2CID 2926575.
[7]
Parsons LH, Weiss F, Koob GF (December 1998). "Serotonin1B receptor stimulation enhances cocaine reinforcement". The Journal of Neuroscience. 18 (23): 10078–10089. doi:10.1523/JNEUROSCI.18-23-10078.1998. PMC 6793270. PMID 9822762.
[8]
Przegalinski E, Filip M, Papla I, Siwanowicz J (April 2001). "Effect of serotonin (5-HT)1B receptor ligands on cocaine sensitization in rats". Behavioural Pharmacology. 12 (2): 109–116. doi:10.1097/00008877-200104000-00004. PMID 11396515.
[9]
Przegaliński E, Gołda A, Frankowska M, Zaniewska M, Filip M (March 2007). "Effects of serotonin 5-HT1B receptor ligands on the cocaine- and food-maintained self-administration in rats". European Journal of Pharmacology. 559 (2–3): 165–172. doi:10.1016/j.ejphar.2006.12.012. PMID 17291490.
[10]
Przegaliński E, Gołda A, Filip M (2008). "Effects of serotonin (5-HT)(1B) receptor ligands on cocaine-seeking behavior in rats". Pharmacological Reports. 60 (6): 798–810. PMID 19211971.
[11]
Tatarczyńska E, Antkiewicz-Michaluk L, Kłodzińska A, Stachowicz K, Chojnacka-Wójcik E (May 2005). "Antidepressant-like effect of the selective 5-HT1B receptor agonist CP 94253: a possible mechanism of action". European Journal of Pharmacology. 516 (1): 46–50. doi:10.1016/j.ejphar.2005.04.025. PMID 15913599.
[12]
Miczek KA, Fish EW, De Bold JF, De Almeida RM (October 2002). "Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems". Psychopharmacology (Berl). 163 (3–4): 434–458. doi:10.1007/s00213-002-1139-6. PMID 12373445.
[13]
Bell R, Donaldson C, Gracey D (September 1995). "Differential effects of CGS 12066B and CP-94,253 on murine social and agonistic behaviour". Pharmacol Biochem Behav. 52 (1): 7–16. doi:10.1016/0091-3057(95)00077-a. PMID 7501681.
[14]
Fish EW, Faccidomo S, Miczek KA (October 1999). "Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT(1B) receptor agonist CP-94,253". Psychopharmacology (Berl). 146 (4): 391–399. doi:10.1007/pl00005484. PMID 10550489.
[15]
Kirilly E, Benko A, Ferrington L, Ando RD, Kelly PA, Bagdy G (February 2006). "Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats". Int J Neuropsychopharmacol. 9 (1): 63–76. doi:10.1017/S146114570500581X. PMID 16060968.
[16]
De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (May 2006). "5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice". Psychopharmacology (Berl). 185 (4): 441–450. doi:10.1007/s00213-006-0333-3. PMID 16550387.
[17]
Bannai M, Fish EW, Faccidomo S, Miczek KA (August 2007). "Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice". Psychopharmacology (Berl). 193 (2): 295–304. doi:10.1007/s00213-007-0780-5. PMID 17440711.
[18]
Fish EW, McKenzie-Quirk SD, Bannai M, Miczek KA (March 2008). "5-HT(1B) receptor inhibition of alcohol-heightened aggression in mice: comparison to drinking and running". Psychopharmacology (Berl). 197 (1): 145–156. doi:10.1007/s00213-007-1017-3. PMID 18071678.
[19]
Wang L, Clark EA, Hanratty L, Koblan KS, Foley A, Dedic N, Bristow LJ (December 2024). "TAAR1 and 5-HT1B receptor agonists attenuate autism-like irritability and aggression in rats prenatally exposed to valproic acid". Pharmacol Biochem Behav. 245 173862. doi:10.1016/j.pbb.2024.173862. PMID 39197535.
[20]
Scott SN, Garcia R, Powell GL, Doyle SM, Ruscitti B, Le T, et al. (October 2021). "5-HT_1B receptor agonist attenuates cocaine self-administration after protracted abstinence and relapse in rats". Journal of Psychopharmacology. 35 (10): 1216–1225. doi:10.1177/02698811211019279. PMID 34049460. S2CID 235243643.

CP-94253

See also

References

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