Modulation of morphine-induced antinociception in mice by histamine H3-receptor ligands

Abstract

The effects of compounds active at histamine H3-receptors on morphine-induced antinociception have been investigated in thermal and chemical tests in mice; tail-immersion (50 degrees C) and hot-plate (49 degrees and 55 degrees C) tests and acetic acid-induced writhing. Neither (R)alpha-methylhistamine, a specific agonist, (S)alpha-methylhistamine, a chemical control, nor thioperamide, an antagonist, had any antinociceptive action alone but thioperamide (3 mg kg-1) attenuated the effects of morphine in the tail-immersion test while (R)alpha-methylhistamine (1 mg kg-1), but not the (S) isomer, potentiated its effects in the hot-plate test at 55 degrees C. These results are consistent with the morphine potentiation seen with H1-antagonists and suggest that central histaminergic mechanisms can modulate opioid actions.

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice

“…In fact, it has been reported that H 3 Rs were involved in the reinforcing properties of certain drugs of abuse, such as, morphine [41], cocaine [10,42], amphetamine [10,43], nicotine [44], and 3,4-methylenedioxymethamphetamine "MDMA" [45]. More particularly, the present findings were in agreement with numerous studies that have demonstrated a relationship between H 3 R and alcohol abuse [2][3][4][5][6]46,47].…”

H3 Receptors and Pain Modulation: Peripheral, Spinal, and Brain Interactions

“…In mice, low systemic doses (1-5 mg/kg) are inactive (Owen et al, 1994;Suzuki et al, 1994), but higher doses (5-30 mg/kg) produce dose-dependent, mild antinociceptive effects (Malmberg-Aiello et al, 1994;Farzin et al, 2002). These treatments do not impair motor balance in the rotorod test, suggesting a pain-relieving profile (Farzin et al, 2002).…”

Antagonism of Supraspinal Histamine H3 Receptors Modulates Spinal Neuronal Activity in Neuropathic Rats

“…The H 3 receptor is localized to key sites in the nociceptive system such as the dorsal horn of the spinal cord and several supraspinal regions including the locus coeruleus (LC) (Pillot et al, 2002;Korotkova et al, 2005;Cannon et al, 2007;Medhurst et al, 2008). Although there has been some conflicting pharmacological data with H 3 agonists and a nonselective antagonist (Owen et al, 1994;Farzin et al, 2002;Cannon and Hough, 2005), more recent data with selective H 3 receptor antagonists demonstrate a consistent level of efficacy in reducing allodynia and hyperalgesia in models of neuropathic, osteoarthritic, and inflammatory pain (Medhurst et al, 2007(Medhurst et al, , 2008Hsieh et al, 2010).…”