title: 5-HT6 receptor antagonist attenuates the memory deficits associated with neuropathic pain and improves the efficacy of gabapentinoids.
abstract: BACKGROUND
  Memory deficit is a co-morbid disorder in patients suffering from neuropathic pain. Gabapentin and pregabalin (gabapentinoids) are among the widely prescribed medications for the treatment of neuropathic pain. Memory loss and sedation are the commonly reported side effects with gabapentinoids. Improving the cognitive functions and attenuating drug-induced side effects may play a crucial role in the management of pain.
  
  
  METHODS
  We evaluated the effects of 5-HT6 receptor antagonists on the memory deficits associated with neuropathy. We also studied the effects of 5-HT6 receptor antagonists on the side effects, and the analgesic effects of gabapentinoids.
  
  
  RESULTS
  5-HT6 receptor antagonists attenuated the cognitive deficits in neuropathic rats. Neuropathic rats co-treated with 5-HT6 receptor antagonist and gabapentinoids showed improvement in memory. 5-HT6 receptor antagonists enhanced the analgesic effects of gabapentinoids but had no effect on the motor side effects. The observed effects may not be due to pharmacokinetic interactions.
  
  
  CONCLUSIONS
  5-HT6 receptor antagonist attenuate the cognitive deficits associated with neuropathy, and this effect is also seen when co-treated with gabapentinoids. Since, 5-HT6 antagonists improved the effectiveness of gabapentinoids, reduction in the dosage and frequency of gabapentinoids treatment may reduce the side effects. Combining 5-HT6 receptor antagonist with gabapentinoids may offer a novel treatment strategy for neuropathic pain.
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India; Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Jayarajan
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India. Electronic address: nvsrk@suven.com.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nirogi
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Shinde
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Goura
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India.
authors.forename: Vuyyuru Arun
authors.initials: VA
authors.lastname: Babu
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India.
authors.forename: Sumanth
authors.initials: S
authors.lastname: Yathavakilla
authors.affiliation: Discovery Research, Suven Life Sciences Ltd., Hyderabad - 500 055, India.
authors.forename: Gopinadh
authors.initials: G
authors.lastname: Bhyrapuneni
mesh_terms: D000588:Amines / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D003071:Cognition / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000077206:Gabapentin; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D009437:Neuralgia / Q000150:complications* / Q000523:psychology; D000069583:Pregabalin / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
keywords: 5-HT6 receptor antagonist; Gabapentinoids; Memory; Neuropathy; Rotarod