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Maj J, Gancarczyk L, Goraszczyk E, Rawlow A. 
“Doxepin as a Blocker of Central Serotonin Receptors”. 
Pharmacopsychiat.. 1977;10(6):318-24.
The central anti-serotonin activity of doxepin (DX, Pfizer) was studied. The central anti-serotonin activity of DX was investigated using 3 tests: the 'behavioral syndrome' elicited by serotonin (5-HTP, Sigma-Chem.), the flexor reflex of the hind limb of the spinal rat; and body temperature in rabbits. In mice and rats DX antagonized the 5-HTP induced behavioral syndrome, the ED5O for rats and mice was 4.43 and 3.22 mg/kg respectively. The 5HTP effect was also blocked by imipramine (Polfa), ED50 values were 16 mg/kg for rats and 12.8 mg/kg for mice. Atropine (2.5 5, and 10 mg/kg) did not affect the 5-HTP-induced syndrome. At 5, 10, 25, and 50 mg/kg, DX had no influence on the pinna reflex in rats and mice. At 100 mg/kg DX abolished the righting reflex and was lethal for some animals. At up to 40 mg/kg, imipramine did not change the pinna reflex in rats. DX (2 mg/kg i.v.) did not affect the flexor reflex of the spinal rat, but blocked the stimulation induced by 1 mg/kg i.v., fenfluramine (Servier), 9 mg/kg i.v. LSD (Spofa) or 3 mg/kg i.v. mescaline (Fluke). DX (3-10 mg/kg did not affect the flexor reflex, although a depression of the flexor reflex was occasionally observed after a dose of 10 mg/kg DX. Fenfluramine (lO mg/kg i.v.) induced hyperthermia, which was inhibited by 3 mg/kg i.v. DX; 6 mg/kg DX also blocked hyperthermia induced by 150mcg/kg LSD. At 3, 6, 12 and 24 mg/kg i.p., DX abolished tremor, lacrimation and salivation produced by oxotremorine (l mg/kg i.p.) in mice. The ED50 of DX inhibiting the intensity of temor, lacrimation and salivation was 5, 10.9 and 12.5 mg/kg for each symptom respectively. Like mianserin and danitracen, DX blocks central 5-HT receptors.
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