Prodipine - Wikiwand

Prodipine (INNTooltip International Nonproprietary Name; developmental code name BY-101) is an experimental antiparkinsonian agent of the 4,4-diphenylpiperidine series related to budipine which was never marketed.^[2]^[3]^[1] It was the predecessor of budipine and was similarly found to be effective in the treatment of Parkinson's disease.^[1] However, prodipine produced side effects including gastrointestinal adverse effects, nausea and vomiting, and hypotension.^[1] Due to the nausea and vomiting with the oral form, it could only be tolerated with intravenous administration.^[1] As a result, budipine, which had fewer side effects, was developed instead.^[1]

Other namesBY-101; 1-Isopropyl-4,4-diphenylpiperidine

Routes of
administrationOral, intravenous injection^[1]

Drug classAntiparkinsonian agents

CAS Number

31314-38-2

Quick facts Clinical data, Other names ...

Prodipine
Clinical data

Other names	BY-101; 1-Isopropyl-4,4-diphenylpiperidine
Routes of administration	Oral, intravenous injection^[1]
Drug class	Antiparkinsonian agents
Identifiers
IUPAC name 4,4-diphenyl-1-propan-2-ylpiperidine
CAS Number	31314-38-2
PubChem CID	65775
ChemSpider	59195
UNII	51567MYG7V
ChEMBL	ChEMBL277382
CompTox Dashboard (EPA)	DTXSID20185247
Chemical and physical data
Formula	C₂₀H₂₅N
Molar mass	279.427 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(C)N1CCC(CC1)(C2=CC=CC=C2)C3=CC=CC=C3
InChI InChI=1S/C20H25N/c1-17(2)21-15-13-20(14-16-21,18-9-5-3-6-10-18)19-11-7-4-8-12-19/h3-12,17H,13-16H2,1-2H3 Key:CFOOTBBXHJHHMT-UHFFFAOYSA-N

Pharmacology

The mechanism of action of these drugs is unknown.^[1]^[4] However, budipine is known to stimulate the catecholaminergic system and to increase motor activity and vigilance in animals.^[1] It also increases brain dopamine, norepinephrine, and serotonin levels in animals treated with the monoamine depleting agent reserpine.^[1] It does not affect monoamine oxidase nor does it appear to interact with dopamine D₂ receptors.^[1] Both budipine and prodipine have been described as "central stimulants" in addition to antiparkinsonian agents.^[5] Prodipine is said to have more tendency to induce hyperactivity than budipine.^[1]

Analogues

Besides prodipine and budipine, another close analogue, medipine, was also developed.^[6]^[7]

References

[1]
Przuntek H, Stasch JP (1985). "Biochemical and Pharmacologic Aspects of the Mechanism of Action of Budipine". Clinical Experiences with Budipine in Parkinson Therapy. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 107–112. doi:10.1007/978-3-642-95455-9_15. ISBN 978-3-540-13764-1. Anticholinergics are widely used in addition to target drugs. A preliminary clinical trial (between 1974 and 1976) with prodipine in 161 patients with Parkinson's disease showed excellent to moderate improvement of resting tremor in 60 of the patients, while medication had to be discontinued in 98 patients owing to gastrointestinal side effects and hypotension. [...] Improvement of disability scores [with budipine] (Birkmayer and Neumayer 1972) gave evidence of a dopaminergic action although in some patients side effects were more frequent than with prodipine. [...] Budipine has less tendency to induce hyperactivity than its structural analogue prodipine and so with budipine anxious agitation states are a less frequent side effect. [...] Prodipin (1-isopropyl-4,4-diphenylpiperidine hydrochloride), the precursor of budipine, had already been found superior (unpublished study, Elena Klinik, Kassel, 1977) in this respect in a large number of patients. But the drug had one big disadvantage, it was tolerated on i.v. injection only. Oral doses caused nausea and vomiting and were thus not feasible. We now have high hopes for the product which was further developed, budipine.
[2]
Gerstenbrand F, Poewe W, Stern G (1985). Clinical Experiences with Budipine in Parkinson Therapy. Springer Berlin Heidelberg. pp. 80, 107, 142. ISBN 978-3-642-95455-9. Retrieved 28 September 2024.
[3]
Vidaluc JL (1996). "MPTP as a Molecular Paradigm for Neurodegeneration. A Review of its Connections with Relevant Molecules". Current Medicinal Chemistry. Bentham Science Publishers. pp. 117–138. Retrieved 28 September 2024. Protective effect in the parkinsonian model with MPTP were displayed by prodipine (R=i-Pr) and budipine (R=t-Bu) in the 4,4-diphenylpiperidine series [110].
[4]
Eltze M (1999). "Multiple mechanisms of action: The pharmacological profile of budipine". Diagnosis and Treatment of Parkinson's Disease — State of the Art. Journal of Neural Transmission. Supplementa. Vol. 56. pp. 83–105. doi:10.1007/978-3-7091-6360-3_4. ISBN 978-3-211-83275-2. PMID 10370904. {{cite book}}: |journal= ignored (help)
[5]
"The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances" (PDF). Geneva: World Health Organization. 2018. WHO/EMP/RHT/TSN/2018.1.
[6]
Russ H, Pindur U, Przuntek H (1986). "The interaction of 1-alkyl-4,4-diphenylpiperidines with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine receptor binding site". Journal of Neural Transmission. 65 (3–4): 157–166. doi:10.1007/BF01249078. PMID 3011983. Other representatives of this class of substances, the 1-alkyl-4,4-diphenylpiperidines, such as, e.g., the 1-isopropyl analogue (prodipine) or the 1-methyl analogue (medipine) have similar pharmacological properties including marked tremorin and reserpin antagonism (Schaefer et al., 1984). The mechanism of action of the 1-alkyl-4,4- diphenylpiperidines is not yet understood in detail.
[7]
Fonne-Pfister R, Meyer UA (October 1988). "Xenobiotic and endobiotic inhibitors of cytochrome P-450dbl function, the target of the debrisoquine/sparteine type polymorphism". Biochemical Pharmacology. 37 (20): 3829–3835. doi:10.1016/0006-2952(88)90063-9. PMID 2903741. Budipine (1-t-butyl-4,4-diphenylpiperidine) (Parkinson's disease treatment); Prodipine (1-isopropyl-4,4-diphenylpiperidine); Medipine (1-methyl-4,4-diphenylpiperidine)

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