Inibidor de recaptação de serotonina-noradrenalina-dopamina: diferenças entre revisões

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(Criada por tradução da página "Serotonin–norepinephrine–dopamine reuptake inhibitor")
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Revisão das 18h46min de 8 de maio de 2021

Um inibidor de recaptação de serotonina-noradrenalina-dopamina ( SNDRI ), também conhecido como inibidor de recaptação tripla ( TRI ), é um tipo de droga que atua como um inibidor de recaptação combinado dos neurotransmissores monoamina serotonina, norepinefrina e dopamina . Ele faz isso inibindo concomitantemente o transportador de serotonina (SERT), o transportador de noradrenalina (NET) e o transportador de dopamina (DAT), respectivamente. A inibição da recaptação desses neurotransmissores aumenta suas concentrações extracelulares e, portanto, resulta em aumento da neurotransmissão serotonérgica, adrenérgica e dopaminérgica.

SNDRIs foram desenvolvidos como potenciais antidepressivos e tratamentos para outros transtornos, como obesidade, dependência de cocaína, transtorno de déficit de atenção e hiperatividade (TDAH) e dor crônica . Eles são uma extensão dos inibidores seletivos da recaptação da serotonina (SSRIs) e inibidores da recaptação da serotonina-norepinefrina (IRSNs) em que se acredita que a adição da ação dopaminérgica tem a possibilidade de aumentar o benefício terapêutico. No entanto, os efeitos colaterais aumentados e o potencial de abuso são preocupações potenciais desses agentes em relação aos seus homólogos SSRI e SNRI.

Indicações

Depressão

O transtorno depressivo maior (TDM) é a principal razão que apóia a necessidade de desenvolvimento de um SNDRI. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] De acordo com a Organização Mundial da Saúde, a depressão é a principal causa de deficiência e o quarto maior contribuinte para a carga global de doenças em 2000. Até o ano de 2020, projeta-se que a depressão alcance o 2º lugar no ranking de DALYs . [11]

Farmacoterapia

Permanece a necessidade de agentes antidepressivos mais eficazes. Embora dois terços dos pacientes respondam ao tratamento antidepressivo, um terço dos pacientes responde ao placebo, [12] e a remissão é freqüentemente submáxima ( sintomas residuais ). Além da recaída pós-tratamento, os sintomas depressivos podem até mesmo reaparecer no decorrer da terapia de longo prazo ( taquifilaxia ). Além disso, todos os antidepressivos disponíveis atualmente provocam efeitos colaterais indesejáveis, e novos agentes devem ser despojados dos efeitos colaterais desagradáveis dos antidepressivos de primeira e segunda geração. [6]

Outras

Lista de SNDRIs

Produtos farmacêuticos aprovados

A sibutramina é um anorexígeno que atua como um SNDRI in vitro.[19] No entanto, evidências limitadas sugerem que a sibutramina atua também como um pró-fármaco in vivo, produzindo metabólitos mais potentes.[20][21]

A venlafaxina (Effexor) às vezes é chamada de SNDRI, mas seu perfil de ligação proteica é extremamente desbalaceado. [22] Pode inibir fracamente a recaptação de dopamina em altas doses. [23]

Fármacos com atividade SNDRI fraca

Ensaios clínicos em andamento

  • Amitifadina (DOV-21.947, EB-1010) (2003) [29] [30] [31]
  • AN788 (anteriormente NSD-788) - veja aqui para detalhes
  • Ansofaxina (LY03005 / LPM570065) [32]
  • Centanafadina (EB-1020) - veja aqui os detalhes da proporção de 1 a 6 a 14 para NDS
  • Dasotralina (SEP-225,289) [5][33][34]
  • Lu AA34893 - veja aqui (modulador SNDRI e 5-HT 2A, α 1 e 5-HT 6 )
  • Lu AA37096 - veja aqui (modulador SNDRI e 5-HT 6 )
  • NS-2360 - principal metabólito de tesofensina
  • Tedatioxetina (Lu AA24530) - SNDRI e modulador 5-HT 2C, 5-HT 3, 5-HT 2A e α 1 [35] [36]
  • Tesofensina (NS-2330) (2001)

Ensaios clínicos interrompidos

  • Bicifadina (DOV-220.075) - interrompido em 1981[37][38]
  • BMS-866.949
  • Brasofensina (NS-2214, BMS-204,756) (1995) [39]
  • Diclofensina (Ro 8-4650) (1982)[40][41]
  • DOV-216.303 (2004)[42][43]
  • EXP-561 (1965)[44]
  • Liafensina (BMS-820.836)
  • NS-2359 (GSK-372.475)[45]
  • RG-7166 (2009–2012)

Drogas projetadas

  • 3-Metil-PCPy[46]
  • Nafirona (O-2482, naftilpirovalerona, NRG-1) (2006) [47] [48] [49]

Compostos pesquisados (não testados em humanos)

  • 3,3-Difenilciclobutanamina (1978)[50]
  • 3,4-Diclorotametralina (trans-(1R,4S)-sertralina ) (1980)[51]
  • D-161 (2008)[52]
  • Desmetilsertralina - metabólito ativo da sertralina; afinidade 76 nM para SERT, 420 nM para NET, 440 nM para DAT[53]
  • DMNPC (2000)[54]
  • DOV-102.677 (2006–2011)[13]
  • GSK1360707F (2010) [55] [56]
  • Indatralina (1985)[57]
  • JNJ-7925476 (2008; apareceu pela primeira vez em 1987) [58]
  • JZ-IV-10 (2005)[59]
  • JZAD-IV-22 (2010)[60]
  • LR-5182 (1978)[61][62][63]
  • Metilnaftidato (HDMP-28) (2001)[64]
  • MI-4[65][66]
  • PRC200-SS (2008)[67]
  • SKF-83.959 (2013)[68]
  • TP1 (2011)[69]
  • Vários feniltropanos, como WF-23, dicloropano e RTI-55[70]
  • NS9775 [71]

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