Melperon

Structural formula
General
Non-proprietary name	Melperon
other names	4-fluoro-4- (4-methyl-piperidino) butyrophenone
Molecular formula	C 16 H 22 FNO
External identifiers / databases
ECHA InfoCard	100.107.027
PubChem	15387
ChemSpider	14646
DrugBank	DB09224
Wikidata	Q415972
Drug information
ATC code	N05 AD03
Drug class	Neuroleptic; Butyrophenones;
Mechanism of action	Blockade of postsynaptic D2 receptors in the mesolimbic or mesocortical system
properties
Molar mass	263.35 g · mol -1
Physical state	firmly
Melting point	209–211 ° C (Melperon hydrochloride )
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-312-332-319
	P: 201-261-271-280
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Melperon is a neuroleptic from the class of butyrophenones . Pharmacologically , it is assigned to the typical neuroleptics. The antipsychotic potency (reference is chlorpromazine ) is inferior to the sedative component. It is mainly used for states of excitement, tension and sleep disorders. Melperon has a very low incidence of so-called EPS ( extrapyramidal disorders ), compared with other medium- and low-potency neuroleptics , it has a low impact on the cardiovascular system and a very low delirium- inducing effect, so that it is often used in gerontopsychiatric patients.

pharmacology

Indications

As already mentioned, Melperon v. a. Use for excitement, tension and sleep disorders (doses of 10–100 mg / day or at night), but it is also used for states of confusion and alcoholic delirium (doses of 50–200 mg / day). Another indication is an additional medication for anxious-depressive patients with possible sleep disorders (doses 25–75 mg / day or at night). An antipsychotic ( counteracting positive symptoms ) effect is only achieved with high doses (approx. 200–400 mg / day), but Melperon is rarely used in this indication.

Pharmacodynamics

Melperon has a relatively weak antidopaminergic effect by blocking postsynaptic D ₂ receptors in the mesolimbic or mesocortical areas; Medium to high affinity and binding only for a short time (so-called “hit-and-run effect”); In the nigrostriatal region, the D ₂ antagonism is even lower, hence the low incidence of EPS. Serotonin blockade also contributes to the effect.

Melperon also has a marked anti-adrenergic effect ( α ₁ blockade), which probably contributes to the sedative effect, but this is short-term and the possible hypotensive effect is only weak.

Pharmacokinetics

Melperon is rapidly and almost completely absorbed after oral administration and is subject to a high first-pass effect. c _max is reached within 1–3 hours; Distribution volume V _d = approx. 7–10 l · kg ⁻¹ , plasma protein binding approx. 50%, half-life T _{β (1/2)} = approx. 6–8 hours (steady state). Melperon is rapidly and almost completely metabolised in the liver. The elimination occurs primarily renally (through the kidneys ), mostly as metabolites (intensive metabolism).

unwanted effects

As with other neuroleptics, the side effects of Melperon include anticholinergic effects.

Manufacturing

The synthesis takes place from 4-methylpiperidine and 4-chloro-4'-fluorobutyrophenone by a nucleophilic substitution .

Trade names

Monopreparations

Buronil (A), Melneurin (D), Eunerpan (D), numerous generics (D), Bunil (P)

Individual evidence

^ The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1006, ISBN 978-0-911910-00-1 .
↑ ^a ^b Registration dossier on 1- (4-fluorophenyl) -4- (4-methylpiperidin-1-yl) butan-1-one ( GHS section ) at the European Chemicals Agency (ECHA), accessed on July 7, 2020.
↑ Technical information for Melperon. Retrieved January 8, 2018 .
↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 511.
^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances , 4th edition (2000), 2 volumes published by Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.

:

[MERCK_Index-1] The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals , 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; P. 1006, ISBN 978-0-911910-00-1 .

[Registrierungsdossier-2] Registration dossier on 1- (4-fluorophenyl) -4- (4-methylpiperidin-1-yl) butan-1-one ( GHS section ) at the European Chemicals Agency (ECHA), accessed on July 7, 2020.

[3] Technical information for Melperon. Retrieved January 8, 2018 .

[4] Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 511.

[A._Kleemann-5] Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances , 4th edition (2000), 2 volumes published by Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.