ITRM20080436A1 - USE OF THE FINASTERIDE AND OTHER INHIBITING SUBSTANCES OF THE ENZYME 5-A-REDUTTASI FOR THE PREVENTION AND CARE OF THE IMPULSE AND AGGRESSIVE DISTURBANCES - Google Patents
USE OF THE FINASTERIDE AND OTHER INHIBITING SUBSTANCES OF THE ENZYME 5-A-REDUTTASI FOR THE PREVENTION AND CARE OF THE IMPULSE AND AGGRESSIVE DISTURBANCESInfo
- Publication number
- ITRM20080436A1 ITRM20080436A1 IT000436A ITRM20080436A ITRM20080436A1 IT RM20080436 A1 ITRM20080436 A1 IT RM20080436A1 IT 000436 A IT000436 A IT 000436A IT RM20080436 A ITRM20080436 A IT RM20080436A IT RM20080436 A1 ITRM20080436 A1 IT RM20080436A1
- Authority
- IT
- Italy
- Prior art keywords
- finasteride
- enzyme
- aggression
- impulse
- aggressive
- Prior art date
Links
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 title claims description 25
- 229960004039 finasteride Drugs 0.000 title claims description 25
- 108090000790 Enzymes Proteins 0.000 title claims description 21
- 102000004190 Enzymes Human genes 0.000 title claims description 21
- 239000000126 substance Substances 0.000 title claims description 10
- 230000002265 prevention Effects 0.000 title claims description 6
- 230000002401 inhibitory effect Effects 0.000 title description 5
- 230000016571 aggressive behavior Effects 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 21
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 claims description 4
- 229960004199 dutasteride Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 description 21
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 9
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
- 229960003604 testosterone Drugs 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 4
- 239000002532 enzyme inhibitor Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229960003878 haloperidol Drugs 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 3
- 206010001488 Aggression Diseases 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 230000002539 anti-aggressive effect Effects 0.000 description 3
- 229960004046 apomorphine Drugs 0.000 description 3
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000003176 neuroleptic agent Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 230000001548 androgenic effect Effects 0.000 description 2
- 229960003473 androstanolone Drugs 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- AURFZBICLPNKBZ-SYBPFIFISA-N brexanolone Chemical compound C([C@@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-SYBPFIFISA-N 0.000 description 2
- 229940052760 dopamine agonists Drugs 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000000506 psychotropic effect Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 1
- XMRPGKVKISIQBV-BJMCWZGWSA-N 5alpha-pregnane-3,20-dione Chemical compound C([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 XMRPGKVKISIQBV-BJMCWZGWSA-N 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 206010010219 Compulsions Diseases 0.000 description 1
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
- 208000001613 Gambling Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000030990 Impulse-control disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 206010034158 Pathological gambling Diseases 0.000 description 1
- AURFZBICLPNKBZ-UHFFFAOYSA-N Pregnanolone Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(=O)C)C1(C)CC2 AURFZBICLPNKBZ-UHFFFAOYSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010042008 Stereotypy Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 201000002996 androgenic alopecia Diseases 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 229940094957 androgens and estrogen Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000001090 anti-dopaminergic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 206010003883 azoospermia Diseases 0.000 description 1
- 230000006741 behavioral dysfunction Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- DUSHUSLJJMDGTE-ZJPMUUANSA-N cyproterone Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DUSHUSLJJMDGTE-ZJPMUUANSA-N 0.000 description 1
- 229960003843 cyproterone Drugs 0.000 description 1
- ZESRJSPZRDMNHY-UHFFFAOYSA-N de-oxy corticosterone Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 ZESRJSPZRDMNHY-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 229940119740 deoxycorticosterone Drugs 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229960000632 dexamfetamine Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 201000000079 gynecomastia Diseases 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 238000006241 metabolic reaction Methods 0.000 description 1
- 230000001730 monoaminergic effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 208000008634 oligospermia Diseases 0.000 description 1
- 230000036616 oligospermia Effects 0.000 description 1
- 231100000528 oligospermia Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007119 pathological manifestation Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000022821 personality disease Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000079 pharmacotherapeutic effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001141 propulsive effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000003236 psychic effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000010009 steroidogenesis Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Description
Descrizione dell'invenzione industriale avente per titolo: “Uso della finasteride e di altre sostanze inibenti l'enzima 5-a-reduttasi per la prevenzione e la cura dei disturbi dell’impulso e dell'aggressività” Description of the industrial invention entitled: "Use of finasteride and other substances inhibiting the 5-a-reductase enzyme for the prevention and treatment of impulse and aggression disorders"
La presente invenzione riguarda l'uso della finasteride e di altre sostanze inibenti l'enzima 5-a-reduttasi per la prevenzione e la cura dei disturbi dell’impulso e dell'aggressività. The present invention relates to the use of finasteride and other substances inhibiting the 5-a-reductase enzyme for the prevention and treatment of impulse and aggression disorders.
William James, nel suo trattato fondante la psicologia dell’era moderna dedicò 150 anni fa al problema dell’impulsività soltanto 2 pagine su oltre 1300. Da tempo tuttavia la dimensione sociale legata a problemi connessi all’impulsività come quelli dell’aggressione violenta sono diventati ima delle emergenze della società moderna. Tali disturbi non sono connotati da questa o quella patologia mentale o neurologica ma, profondamente ed oscuramente ancorate alla natura umana, appaiono emergere in soggetti apparentemente normali che solo raramente sono inquadrabili in determinate patologie. Tuttavia, la base biochimica che dovrebbe contribuire a queste disfunzioni comportamentali sta cominciando ad essere capita meglio anche se al giorno d’oggi, il trattamento farmacologico dell’aggressività, presa come paradigma dei disturbi del controllo degli impulsi, è ancora ampiamente basato su farmaci la cui sintesi è avvenuta negli anni ’ 50 ed il cui uso principale è quello delle psicosi. Tali farmaci, noti come neurolettici, o tranquillanti maggiori, presentano un'impressionante sequenza di effetti collaterali, tanto che negli anni ’70 venne per essi coniato il termine di “camicia di forza chimica”. E’ chiaro che farmaci siffatti, pur nel loro perfezionamento recente, per gli effetti collaterali sul sistema motorio e sulle associazioni del pensiero, possono essere riservati a soggetti affetti da patologie psicotiche nei quali Γ aggressività in particolare ed i disturbi deH’impulso in generale, ad esempio spesa compulsiva o gioco d’azzardo patologico, sono tra le manifestazioni di un grave stato di alterazione delle attività psichiche che costituisce il principale bersaglio del farmaco poiché l’aggressività è uno dei sintomi di una profonda destrutturazione esistenziale causata dalla malattia. Ma l’impatto socio-economico di tutti i casi di aggressione violenta in Italia e negli altri paesi occidentali non è attribuibile che per una piccolissima parte ai casi sopra citati che, anzi, se trattati adeguatamente con neurolettici, dovrebbero, e di fatto è così, costituire appunto una percentuale trascurabile del problema. Al contrario, i disturbi dell’impulso ha raggiunto dimensioni altamente preoccupanti. William James, in his founding treatise on the psychology of the modern era, dedicated 150 years ago to the problem of impulsivity only 2 pages out of over 1300. For some time, however, the social dimension linked to problems related to impulsivity such as those of violent aggression have become ima of the emergencies of modern society. These disorders are not connoted by this or that mental or neurological pathology but, deeply and obscurely anchored to human nature, appear to emerge in apparently normal subjects who only rarely can be classified in certain pathologies. However, the biochemical basis that is supposed to contribute to these behavioral dysfunctions is beginning to be better understood even though nowadays, the drug treatment of aggression, taken as the paradigm of impulse control disorders, is still largely drug-based. whose synthesis took place in the 1950s and whose main use is that of psychosis. These drugs, known as neuroleptics, or major tranquilizers, have an impressive sequence of side effects, so much so that in the 1970s the term "chemical straitjacket" was coined for them. It is clear that such drugs, despite their recent improvement, for side effects on the motor system and on thought associations, can be reserved for subjects suffering from psychotic pathologies in which aggressiveness in particular and impulse disorders in general. for example, compulsive spending or pathological gambling, are among the manifestations of a severe state of alteration of psychic activities which is the main target of the drug since aggression is one of the symptoms of a profound existential destructuring caused by the disease. But the socio-economic impact of all cases of violent aggression in Italy and in other Western countries is attributable only for a very small part to the cases mentioned above which, indeed, if treated adequately with neuroleptics, should, and in fact it is so , constitute a negligible percentage of the problem. On the contrary, impulse disturbances have reached highly worrying dimensions.
Diversi studi confermano un progressivo aumento dei crimini legati ad atti di violenza presso diverse fasce di popolazione, ma soprattutto in quella adolescenziale. A partire dagli anni ’70, le serie conseguenze sociologiche dell’ aggressività hanno spinto la comunità scientifica ad approfondire gli studi sulle sue cause psicologiche e neurobiologiche, nonché sulle connotazioni culturali che ne modulano l’espressione. Several studies confirm a progressive increase in crimes linked to acts of violence in different segments of the population, but especially in adolescents. Since the 1970s, the serious sociological consequences of aggression have prompted the scientific community to deepen studies on its psychological and neurobiological causes, as well as on the cultural connotations that modulate its expression.
Nel ridefinire le valenze etologiche dei fenomeni di aggressività e dominanza nel contesto sociale, questi studi hanno anche contribuito a stabilire una serie di nuovi criteri di classificazione nosografica delle manifestazioni aberranti e patologiche dell’aggressività, sottolineando l’importanza di adeguate strategie psico- e farmacoterapeutiche per la loro gestione. In redefining the ethological values of the phenomena of aggression and dominance in the social context, these studies have also contributed to establishing a series of new nosographic classification criteria for the aberrant and pathological manifestations of aggression, underlining the importance of adequate psycho- and pharmacotherapeutic strategies. for their management.
Recenti tavole rotonde e convegni incentrati su queste tematiche hanno sottolineato come tratti aggressivi patologici rientrino frequentemente nella sintomatologia di una vasta ed eterogenea gamma di disturbi di personalità di difficile inquadramento, nella quale l’impulsività patologica esplode nell’aggressione violenta. Recent round tables and conferences focusing on these issues have emphasized how aggressive pathological traits frequently fall within the symptomatology of a vast and heterogeneous range of difficult to classify personality disorders, in which pathological impulsivity explodes in violent aggression.
Al di là dei problemi ferapeiitici scaturenti dalla comorbidità dei tratti aggressivi con altri disturbi - l’aggressività nei pazienti psichiatrici è spesso collegata ad un generale deterioramento cognitivo e sintomatologico ed è fónte ricorrente di peggioramento della compliance del paziente al trattamento - la condotta aggressiva comporta difficoltà decisionali legate all’opportunità dell’utilizzo. di atti di forza e di contenzione coatta che minano alla base il rapporto medicopaziente ed hanno un impatto negativo sul personale infermieristico e paramedico. Al contrario, come già accennato, la gestione dell’aggressività con farmaci neurolettici è ancora generalmente deludente, a causa dei gravi effetti collaterali. Beyond the ferapeiitic problems arising from the comorbidity of aggressive traits with other disorders - aggression in psychiatric patients is often linked to a general cognitive and symptomatic deterioration and is a recurrent source of worsening of the patient's compliance with treatment - aggressive conduct involves difficulties decision-making related to the appropriateness of use. of acts of force and forced restraint that undermine the doctor-patient relationship and have a negative impact on the nursing and paramedical staff. On the contrary, as already mentioned, the management of aggression with neuroleptic drugs is still generally disappointing, due to the serious side effects.
Una strategia terapeutica alternativa recentemente proposta da alcuni autori riguarda l’attenuazione degli effetti del testosterone e degli ormoni androgeni. L’iniziale osservazione di una più alta incidenza di aggressività nella popolazione maschile ha condotto alla dimostrazione che il testosterone aumenta questo tratto comportamentale probabilmente interferendo con le funzioni monoaminergiche, in particolare, dopaminergiche e serotoninergiche, che ne modulano l’espressione. An alternative therapeutic strategy recently proposed by some authors concerns the attenuation of the effects of testosterone and androgens. The initial observation of a higher incidence of aggression in the male population led to the demonstration that testosterone increases this behavioral trait probably by interfering with monoaminergic functions, in particular, dopaminergic and serotonergic functions, which modulate its expression.
Alcuni studi hanno recentemente proposto l’utilizzo nella terapia antiaggressiva di farmaci come la flutamide e il ciproterone, che bloccano i recettori endocellulari fisiologicamente attivati dal testosterone. Nonostante i risultati clinici di queste ricerche siano incoraggianti, i gravi effetti collaterali di questi farmaci, quali impotenza, ejpato- e cardiotossicità, notevoli alterazioni degli equilibri ormonali, ne limitano pesantemente l’uso in regime cronico. Some studies have recently proposed the use in anti-aggression therapy of drugs such as flutamide and cyproterone, which block intracellular receptors physiologically activated by testosterone. Although the clinical results of these researches are encouraging, the serious side effects of these drugs, such as impotence, hepato- and cardiotoxicity, significant alterations in hormonal balances, severely limit their use in a chronic regime.
Pertanto, in alternativa ai farmaci citati nell'introduzione di questa descrizione, che bloccano i recettori endocellulari fisiologicamente attivati dal testosterone^viene proposto, secondo l'invenzione, l'impiego di farmaci che _ esercitano un'azione antiandrogenica senza gravi effetti collaterali attraverso l'inibizione dell'enzima 5AR. Therefore, as an alternative to the drugs cited in the introduction of this description, which block the endocellular receptors physiologically activated by testosterone, the use of drugs is proposed, according to the invention, which exert an antiandrogenic action without serious side effects through the inhibition of the 5AR enzyme.
Infatti, come è noto, il testosterone subisce due principali destini metabolici nel sistema nervoso centrale. Esso è infatti convertito in diidrotestosterone (DHT), il più potente androgeno neuroattivo, dall'enzima 5-a-reduttasi (5AR), e in βestradiolo, il principale estrogeno, dall'enzima animatasi. Diverse ricerche hanno evidenziato che la maggior parte delle azioni psicotrope androgeniche del testosterone sono in realtà mediate dal DHT. Inoltre, numerose ricerche suggeriscono che androgeni ed estrogeni abbiano effetti opposti sull’aggressività maschile. Inoltre, queste premesse indicano che la via metabolica dell'enzima 5AR gioca un ruolo cruciale nella patogenesi dell’aggressività, suggerendo che l’inibizione di questo enzima potrebbe essere un'efficace strategia nel controllo dell'aggressività. Ad oggi, sono state caratterizzate due isoforme dell'enzima 5AR, entrambe coinvolte nella conversione di diversi precursori steroidei contenenti un doppio legame a steroidi 5-a idrogenati. I due isoenzimi differiscono, tra gli altri aspetti, per la diversa localizzazione: nell’adulto, il tipo 1 è prevalente nel sistema nervoso centrale, mentre l’espressione dell'enzima 5AR tipo 2 è significativamente piu’ alta negli organi periferici bersaglio, come la prostata e le gonadi. Le differenze funzionali esistenti tra le due isoforme dell'enzima 5AR non sono tuttavia ancora chiare. La maggior parte degli studi sull'enzima 5AR riguarda due reazioni metaboliche: la riduzione del progesterone in 5-a-pregnano-3,20-dione (5-a DHP), il precursore immediato del 3-a-idrossi-5-a-pregnano-20-one (allopregnanolone), e la conversione del testosterone in DHT. Peraltro, altre reazioni sono catalizzate da questo enzima, come la riduzione del deossicorticosterone in 5-a-diidrodeossicorticosterone, come evidenziato nella sottostante Figura 1. Questa figura, che descrive schematicamente il molo dell'enzima 5-a-reduttasi nella steroidogenesi, è tratta da Annals of thè NewYork Academy of Sciences, 2003, Voi. 1007, pagine 64-78. In fact, as is known, testosterone undergoes two main metabolic fates in the central nervous system. It is in fact converted into dihydrotestosterone (DHT), the most powerful neuroactive androgen, by the enzyme 5-a-reductase (5AR), and into βestradiol, the main estrogen, by the enzyme animatase. Several researches have shown that most of the psychotropic androgenic actions of testosterone are actually mediated by DHT. Furthermore, numerous researches suggest that androgens and estrogens have opposite effects on male aggression. Furthermore, these premises indicate that the metabolic pathway of the 5AR enzyme plays a crucial role in the pathogenesis of aggression, suggesting that inhibition of this enzyme could be an effective strategy in controlling aggression. To date, two isoforms of the 5AR enzyme have been characterized, both of which are involved in the conversion of different steroid precursors containing a double bond to hydrogenated 5-a steroids. The two isoenzymes differ, among other aspects, for the different localization: in adults, type 1 is prevalent in the central nervous system, while the expression of the 5AR type 2 enzyme is significantly higher in peripheral target organs, such as the prostate and gonads. However, the functional differences between the two isoforms of the 5AR enzyme are not yet clear. Most studies of the 5AR enzyme involve two metabolic reactions: the reduction of progesterone to 5-a-pregnane-3,20-dione (5-a DHP), the immediate precursor of 3-a-hydroxy-5-a -pregnan-20-one (allopregnanolone), and the conversion of testosterone to DHT. Moreover, other reactions are catalyzed by this enzyme, such as the reduction of deoxycorticosterone to 5-a-dihydrodeoxycorticosterone, as shown in Figure 1 below. This figure, which schematically describes the role of the 5-a-reductase enzyme in steroidogenesis, is from Annals of the NewYork Academy of Sciences, 2003, Vol. 1007, pages 64-78.
Gli inibitori dell'enzima 5AR sono stati di recente sviluppati e impiegati nella pratica clinica. In particolare, fra questi, il farmaco caratterizzato in modo più approfondito è la finasteride, corrispondente a N-( 1,1 -dimetiletil)-3 -ossi-da, 17P)-4-azaandrost-l-ene-17-carbossamide. La finasteride è stata approvata nel 1992 dalla Food and Drug Administration negli USA per il trattamento dell’ipertrofia prostatica benigna (alla dose di 5 mg/die), e nel 1997 per l’alopecia androgenica (alla dose di 1 mg/die). 5AR enzyme inhibitors have recently been developed and used in clinical practice. In particular, among these, the drug characterized in more detail is finasteride, corresponding to N- (1,1-dimethylethyl) -3 -oxy-da, 17P) -4-azaandrost-1-ene-17-carboxamide. Finasteride was approved in 1992 by the Food and Drug Administration in the USA for the treatment of benign prostatic hypertrophy (at a dose of 5 mg / day), and in 1997 for androgenic alopecia (at a dose of 1 mg / day).
L’utilizzo clinico della finasteride ha dimostrato un’alta tollerabilità di questo ,.farmaco, con scarsi effetti collaterali rilevati in un ristretto numero di pazienti. Gli effetti noti comprendono la diminuzione della libido, difficoltà a raggiungere l’erezione, oligospermia e rare reazioni allergiche. Nonostante alcuni studi abbiano suggerito una minima incidenza di ginecomastia, il dato è controverso.. Nessuna interazione con altri farmaci è stata riportata in letteratura. Inoltre, l’azione del farmaco non è completamente nota nelle femmine. Nonostante alcune sperimentazioni cliniche abbiano dimostrato la sua efficacia nell’irsutismo femminile, l’utilizzo della finasteride è potenzialmente pericoloso in gravidanza per gli effetti di interferenza con le azioni androgeniche in fase di sviluppo di feti maschi. The clinical use of finasteride has shown a high tolerability of this drug, with few side effects detected in a small number of patients. Known effects include decreased libido, difficulty in achieving an erection, oligospermia and rare allergic reactions. Although some studies have suggested a minimal incidence of gynecomastia, the data is controversial. No interactions with other drugs have been reported in the literature. Furthermore, the action of the drug is not fully known in females. Although some clinical trials have shown its effectiveness in female hirsutism, the use of finasteride is potentially dangerous in pregnancy due to the effects of interference with the androgenic actions in the development phase of male fetuses.
Una sperimentazione quinquennale ha comunque mostrato che effetti indesiderati sono stati riscontrati nell’ 1,8% dei pazienti trattati, alla dose di 1 mg/die, contro l’1.3% dei pazienti sotto placebo, a sottolineare la scarsa tossicità del farmaco. Per giunta, gli effetti in questione si sono prontamente risolti con la sospensione della finasteride. È da notare che gli antipsicotici tipici e atipici presentano un’incidenza di effetti sessuali molto più alta di quella riportata per la finasteride, fino al 40% secondo recenti statistiche. However, a five-year trial showed that undesirable effects were found in 1.8% of patients treated, at a dose of 1 mg / day, against 1.3% of patients on placebo, to underline the low toxicity of the drug. In addition, the effects in question were promptly resolved with the suspension of finasteride. It should be noted that typical and atypical antipsychotics have a much higher incidence of sexual effects than that reported for finasteride, up to 40% according to recent statistics.
La fmasteride presenta una maggiore affinità per l'enzima 5AR tipo 2 nel maschio, che è scarsamente rappresentata nel sistema nervoso centrale adulto. Peraltro, diversi autori sostengono che l’efficacia del farmaco nella terapia dell’alopecia sia indicativa della sua attività inibitoria in v/vo anche per l'enzima 5AR tipo 1, l’unica isoforma presente nel bulbo pilifero. Inoltre, recenti studi hanno dimostrato che la fìnasteride possiede una chiara azione psicotropica, potendo indurre depressione in alcuni casi. Fmasteride has a higher affinity for the 5AR type 2 enzyme in males, which is poorly represented in the adult central nervous system. Moreover, several authors argue that the efficacy of the drug in the treatment of alopecia is indicative of its inhibitory activity in v / v or also for the 5AR type 1 enzyme, the only isoform present in the hair bulb. Furthermore, recent studies have shown that fìnasteride has a clear psychotropic action, being able to induce depression in some cases.
In accordo con queste evidsnze, in preliminari studi clinici abbiamo osservatoche la terapia cronica con fìnasteride ha effetti terapeutici in una malattia, come la sindrome di Tourettè, dove la componente del disturbo dell’impulso può essere elevata. In accordance with these findings, in preliminary clinical studies we have observed that chronic therapy with finasteride has therapeutic effects in a disease, such as Tourette's syndrome, where the impulse disturbance component can be high.
Recentemente è stato approvato un nuovo inibitore dell'enzima 5AR, -la dutasteride, attiva in vitro su entrambi gli isoenzimi 5AR, e dotata di azione terapeutica ed effetti collaterali molto simili alla fìnasteride. Altri inibitori dell'enzima 5AR sono attualmente in fase di sviluppo. Recently, a new inhibitor of the 5AR enzyme, dutasteride, active in vitro on both 5AR isoenzymes, has been approved and has a therapeutic action and side effects very similar to fi nasteride. Other inhibitors of the 5AR enzyme are currently under development.
Sulla base di quanto finora evidenziato, l'invenzione propone l'uso di una sostanza inibente l'attività dell'enzima 5-a-reduttasi per la fabbricazione di un medicamento per la prevenzione e la cura dei disturbi dell’impulso e dell'aggressività. On the basis of what has been pointed out so far, the invention proposes the use of a substance inhibiting the activity of the 5-a-reductase enzyme for the manufacture of a medicament for the prevention and treatment of impulse and aggression disorders. .
In particolare, detta sostanza è costituita dalla fìnasteride, o in un'ulteriore forma di realizzazione dell’invenzione detta sostanza è costituita dalla dutasteride. In particular, said substance is constituted by finasteride, or in a further embodiment of the invention said substance is constituted by dutasteride.
I seguenti risultati sperimentali conseguiti sono qui riportati a sostegno della proposta di impiego delle sostanze citate per la prevenzione e la cura dei disturbi deH'impulso e dell'aggressività. The following experimental results are reported here in support of the proposed use of the substances mentioned for the prevention and treatment of impulse and aggression disorders.
Al fine di identificare potenziali attività antiaggressive della finasteride, i suoi effetti sono stati valutati in diversi modelli di aggressione su due diverse specie: topo (Mus musculus) e ratto (Rattus norvegicus) . In order to identify potential antiaggressive activities of finasteride, its effects were evaluated in different models of aggression on two different species: mouse (Mus musculus) and rat (Rattus norvegicus).
In una prima serie di esperimenti, abbiamo valutato l’efficacia della finasteride, in regime acuto e cronico, nel modello murino dell’aggressività di residenti contro intrusi conspecifici (resident-intruder aggression). Questo modello studia il livello di aggressione di un topo maschio nei confronti di un intrusore conspecifico ed è ampiamente validato come modello di aggressione dotato di alta predittività farmacologica. Gli esperimenti con dosi acute hanno dimostrato che, già alla dose di 25 mg/kg (inoculo intraperitoneale), la finasteride produce un significativo decremento dell’aggressività, senza alterare le proprietà motorie dell’animale. Simili risultati si sono ottenuti a seguito di regimi cronici di finasteride (5 mg/kg/al dì for 7 giorni). In a first series of experiments, we evaluated the efficacy of finasteride, in acute and chronic regimen, in the murine model of the aggression of residents against conspecific intruders (resident-intruder aggression). This model studies the aggression level of a male mouse towards a conspecific intruder and is widely validated as an aggression model with high pharmacological predictivity. Experiments with acute doses have shown that, already at a dose of 25 mg / kg (intraperitoneal inoculum), finasteride produces a significant decrease in aggression, without altering the motor properties of the animal. Similar results were obtained following chronic finasteride regimens (5 mg / kg / day for 7 days).
In successivi esperimenti abbiamo dimostrato che dosi acute di finasteride (25 mg/kg, inoculo intraperitoneale) attenuano significativamente Γ aggressività spontanea anche nei topi knock-out per la monoamino-ossidasi A, uno dei modelli transgenici meglio consolidati di aggressione impulsiva. In subsequent experiments we have shown that acute doses of finasteride (25 mg / kg, intraperitoneal inoculum) significantly attenuate spontaneous aggression even in monoamine oxidase A knock-out mice, one of the best established transgenic models of impulsive aggression.
Infine, si è determinato che il trattamento acuto con finasteride riduce significativamente l’aggressività e altri tratti patologici indotti dall’isolamento prolungato (8 settimane) dopo lo svezzamento nei ratti. Questi risultati indicano che il blocco dell'enzima 5AR riduce i comportamenti aggressivi conseguenti a svariate manipolazioni ambientali e suggerisce che gli effetti antiaggressivi osservati possano essere applicabili ad un vasto insieme di disturbi. Finally, it was determined that acute treatment with finasteride significantly reduces aggression and other pathological traits induced by prolonged isolation (8 weeks) after weaning in rats. These results indicate that blocking the 5AR enzyme reduces aggressive behaviors resulting from various environmental manipulations and suggests that the observed antiaggressive effects may be applicable to a wide range of disorders.
In ima diversa serie di esperimenti, si è valutato anche l’impatto della finasteride e della dutasteride in trattamento acuto in modelli animali con validità predittiva per l’aggressività, in confronto con due antipsicotici in clinica, l’aloperidolo e la clozapina. Gli inibitori dell'enzima 5AR hanno ridotto l’iperattività causata dall’agonista dopaminergico indiretto d-amfetamina in maniera dose e tempodipendente e in misura analoga all’aloperidolo. Simili risultati si sono ottenuti sulle stereotipie causate dall’agònista dopaminergico diretto apomorfìna e sulla perdita della propulse inhibition (PPI) del trasalimento acustico (acoustic starile reflex) indotto da amfetamina e apomorfina . In a different series of experiments, the impact of finasteride and dutasteride in acute treatment was also evaluated in animal models with predictive validity for aggression, in comparison with two antipsychotics in the clinic, haloperidol and clozapine. The 5AR enzyme inhibitors reduced the hyperactivity caused by the indirect dopaminergic agonist d-amphetamine in a dose and time dependent manner and to an extent similar to haloperidol. Similar results were obtained on the stereotypies caused by the direct dopaminergic agonist apomorphine and on the loss of the propulsive inhibition (PPI) of acoustic starile reflex induced by amphetamine and apomorphine.
Quest’ultimo modello è àmpiamente validato per la misurazione delle proprietà,di filtro preattentivo delle informazioni (gating), che è generalmente deficitario nelle patologie psicotiche particolarmente in presenza di manifestazioni aggressive. Le ricerche su questo argomento hanno stabilito che anche i pazienti affetti da sindrome di Tourette o disturbo ossessivo-compulsivo presentano in. generale una perdita del gating e una riduzione della PPI. The latter model is extensively validated for the measurement of the properties of a pre-attemptive information filter (gating), which is generally deficient in psychotic pathologies, particularly in the presence of aggressive manifestations. Research on this topic has established that patients with Tourette's syndrome or obsessive-compulsive disorder also present in. general a loss of gating and a reduction in PPI.
A discapito dell’estrema somiglianza di effetti terapeutici tra aloperidolo e inibitori dell'enzima 5AR nelle prove, la finasteride non si lega ai recettori D2 della dopamina, e i due farmaci hanno dimostrato profonde differenze nei test comportamentali relativi agli effetti extrapiramidali, come la catalessia su barra e nel “paw test”. Infatti, la finasteride non ha causato alcun effetto neurolettico anche a dosi elevate. Despite the extreme similarity of therapeutic effects between haloperidol and 5AR enzyme inhibitors in the trials, finasteride does not bind to dopamine D2 receptors, and the two drugs demonstrated profound differences in behavioral tests related to extrapyramidal effects, such as catalepsy on bar and in the "paw test". In fact, finasteride did not cause any neuroleptic effects even at high doses.
Questi risultati hanno mostrato come gli inibitori dell'enzima 5AR abbiano un effetto antidopaminergico che è reminiscente degli effetti dell’ aloperidolo, senza tuttavia presentare gli imponenti effetti collaterali di questo farmaco. Con queste premesse si è pensato che i farmaci che possiedono questa attività possano essere utilizzati come una nuova categoria terapeutica nel trattamento dei disturbi dell’impulso. Inoltre si è osservato un’azione antiaggressiva della finasteride nel trattamento di un giovane affeto da malatia di Tourete dato che gli stessi tic (la manifestazione motoria e vocale prevalente nella sindrome di Tourete) sono stati classicamente considerati da diversi autori come ati di aggressività “introietata”. These results showed that the 5AR enzyme inhibitors have an anti-dopaminergic effect that is reminiscent of the effects of haloperidol, without however presenting the massive side effects of this drug. With these premises it was thought that drugs that possess this activity could be used as a new therapeutic category in the treatment of impulse disorders. Furthermore, an antiaggressive action of finasteride was observed in the treatment of a young person suffering from Tourete's disease since the same tics (the motor and vocal manifestation prevalent in Tourete's syndrome) were classically considered by various authors as ati of "introietate aggression" ".
In tre casi successivi, gli effetti terapeutici della finasteride sono stati confermati, ed è stata sempre riportata una riduzione drammatica delle compulsioni aggressive. In three subsequent cases, the therapeutic effects of finasteride were confirmed, and a dramatic reduction in aggressive compulsions was always reported.
È interessante notare che in tutti gli studi preclinici e clinici-non si sono riscontrati segni evidenti di alterazioni comportamentali alle dosi terapeutiche. Studi preliminari di PPI suggeriscono che l’azione della finasteride contro i ' deficit di gating indotti da apomorfina sono presenti anche in ratti femmina, a prescindere dallo stadio mestruale. Questi risultati potrebbero suggeriscono che la finasteride potrebbe anche avere effeti terapeutici nell’aggressività femminile. Risultati preliminari su alcune sperimentazioni cliniche con agenti antiandrogeni in donne sembrano supportare questa possibilità. It is interesting to note that in all preclinical and clinical studies there were no evident signs of behavioral alterations at therapeutic doses. Preliminary PPI studies suggest that the action of finasteride against apomorphine-induced gating deficits are also present in female rats, regardless of the menstrual stage. These results could suggest that finasteride could also have therapeutic effects in female aggression. Preliminary results on some clinical trials with antiandrogen agents in women seem to support this possibility.
L’enorme vantaggio di trascurabili sintomi collaterali, pari per frequenza a quelli della somministrazione di placebo, rende il farmaco estremamente vantaggioso e certamente di gran lunga più appetibile di una somministrazione di farmaci neurolettici caraterizzati, anche nelle più recenti versioni, da devastanti effetti collaterali. Il farmaco si presta inoltre a consistenti sviluppi successivi di somministrazione (prodotti ritardo, cerotti a vari dosaggi). The enormous advantage of negligible side symptoms, equal in frequency to those of placebo administration, makes the drug extremely advantageous and certainly far more palatable than the administration of neuroleptic drugs characterized, even in the most recent versions, by devastating side effects. The drug also lends itself to consistent subsequent developments of administration (delay products, patches at various dosages).
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT000436A ITRM20080436A1 (en) | 2008-08-06 | 2008-08-06 | USE OF THE FINASTERIDE AND OTHER INHIBITING SUBSTANCES OF THE ENZYME 5-A-REDUTTASI FOR THE PREVENTION AND CARE OF THE IMPULSE AND AGGRESSIVE DISTURBANCES |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT000436A ITRM20080436A1 (en) | 2008-08-06 | 2008-08-06 | USE OF THE FINASTERIDE AND OTHER INHIBITING SUBSTANCES OF THE ENZYME 5-A-REDUTTASI FOR THE PREVENTION AND CARE OF THE IMPULSE AND AGGRESSIVE DISTURBANCES |
Publications (1)
Publication Number | Publication Date |
---|---|
ITRM20080436A1 true ITRM20080436A1 (en) | 2010-02-07 |
Family
ID=40466885
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IT000436A ITRM20080436A1 (en) | 2008-08-06 | 2008-08-06 | USE OF THE FINASTERIDE AND OTHER INHIBITING SUBSTANCES OF THE ENZYME 5-A-REDUTTASI FOR THE PREVENTION AND CARE OF THE IMPULSE AND AGGRESSIVE DISTURBANCES |
Country Status (1)
Country | Link |
---|---|
IT (1) | ITRM20080436A1 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006097970A1 (en) * | 2005-03-18 | 2006-09-21 | Giuseppe La Pera | Use of inhibitors of steroid (testosterone) activity (i. a. estrogens) or antiandrogens) for treatment of substance correlated disorders like drug abuse |
WO2006110557A2 (en) * | 2005-04-07 | 2006-10-19 | Hythiam, Inc. | Methods for the treatment of substance abuse and dependence |
-
2008
- 2008-08-06 IT IT000436A patent/ITRM20080436A1/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006097970A1 (en) * | 2005-03-18 | 2006-09-21 | Giuseppe La Pera | Use of inhibitors of steroid (testosterone) activity (i. a. estrogens) or antiandrogens) for treatment of substance correlated disorders like drug abuse |
WO2006110557A2 (en) * | 2005-04-07 | 2006-10-19 | Hythiam, Inc. | Methods for the treatment of substance abuse and dependence |
Non-Patent Citations (1)
Title |
---|
BORTOLATO MARCO ET AL: "Treatment of Tourette's syndrome with Finasteride", AMERICAN JOURNAL OF PSYCHIATRY, vol. 164, no. 12, December 2007 (2007-12-01), pages 1914 - 1915, XP002522756, ISSN: 0002-953X * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Del Río et al. | Steroid hormones and their action in women's brains: the importance of hormonal balance | |
P Maric et al. | Pharmacological modulation of HPA axis in depression–new avenues for potential therapeutic benefits | |
Jones et al. | The role of monoamine oxidase enzymes in the pathophysiology of neurological disorders | |
Halbreich | The etiology, biology, and evolving pathology of premenstrual syndromes | |
Quines et al. | Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats | |
Witkin et al. | A role for cannabinoid CB1 receptors in mood and anxiety disorders | |
Reddy | Pharmacology of endogenous neuroactive steroids | |
Wainwright et al. | The neural plasticity theory of depression: Assessing the roles of adult neurogenesis and PSA‐NCAM within the hippocampus | |
Sahu et al. | Pharmacological activities of dehydroepiandrosterone: A review | |
Pluchino et al. | Neurobiology of DHEA and effects on sexuality, mood and cognition | |
Benmansour et al. | Comparison of the effects of estradiol and progesterone on serotonergic function | |
Hansen et al. | The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the H295R cell line | |
Haynes et al. | Chronic antidepressant medication attenuates dexamethasone-induced neuronal death and sublethal neuronal damage in the hippocampus and striatum | |
Sethna et al. | From FMRP function to potential therapies for fragile X syndrome | |
Pisu et al. | Neurosteroids and neuroactive drugs in mental disorders | |
AU2010213683B2 (en) | Material and methods for treating developmental disorders including comorbid and idiopathic autism | |
Veeraragavan et al. | The modulation of fragile X behaviors by the muscarinic M4 antagonist, tropicamide. | |
Contreras et al. | Neuronal gene repression in Niemann–Pick type C models is mediated by the c-Abl/HDAC2 signaling pathway | |
Xu et al. | Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway | |
Barron et al. | Reproductive hormones modulate oxidative stress in Alzheimer's disease | |
Menon et al. | Low-dose mirtazapine-induced nightmares necessitating its discontinuation in a young adult female | |
Sierksma et al. | Effects of prenatal stress exposure on soluble Aβ and brain-derived neurotrophic factor signaling in male and female APPswe/PS1dE9 mice | |
Ugale et al. | Essentiality of central GABAergic neuroactive steroid allopregnanolone for anticonvulsant action of fluoxetine against pentylenetetrazole-induced seizures in mice | |
Odetayo et al. | Impact of stress on male fertility: role of gonadotropin inhibitory hormone | |
ITRM20080436A1 (en) | USE OF THE FINASTERIDE AND OTHER INHIBITING SUBSTANCES OF THE ENZYME 5-A-REDUTTASI FOR THE PREVENTION AND CARE OF THE IMPULSE AND AGGRESSIVE DISTURBANCES |