Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate thoroughly the preclinical psychopharmacological profile of venlafaxine, testing a wide range of doses in animal models indicative of antidepressant-like effects. Venlafaxine was found to be active in mouse forced swimming test (at 8, 16, 32 and 64 mg/kg) and to increase spontaneous locomotor activity (at 16, 32 and 64 mg/kg). Venlafaxine antagonised apomorphine-induced (16 mg/kg) hypothermia (at 2, 4, 8, 16, 32 and 64 mg/kg). Pretreatment with PCPA significantly attenuated the anti-immobility effects of venlafaxine (8 and 16mg/kg; P< 0.01) in the mouse forced swimming test. Venlafaxine at a dose of 32 mg/kg remained active, despite PCPA pretreatment. DSP-4 significantly attenuated the anti-immobility effects of venlafaxine (16 mg/kg; P < 0.05), whereas venlafaxine at 32 mg/kg remained active, despite DSP-4 pretreatment. Venlafaxine was active in the forced swimming test when administered at sub-effective doses in combination with (+/-) pindolol (venlafaxine: 1 and 2 mg/kg), RU 24969 (venlafaxine: 1, 2 and 4 mg/kg), 8-OH-DPAT (venlafaxine: 4 mg/kg), clonidine (venlafaxine: 1, 2 and 4 mg/kg), lithium (venlafaxine: 1, 2, and 4 mg/kg) and quinine (venlafaxine: 1 and 2 mg/kg). Prior administration with NAN-190 antagonised the anti-immobility effects of venlafaxine (8, 16 and 32 mg/kg). Interaction studies did not induce changes in locomotor activity. The results of the present study indicated that, at low doses, venlafaxine inhibited serotonin reuptake, while at higher doses it inhibited both serotonin and noradrenaline reuptake.
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PMID:Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity. 969 20

Venlafaxine (VEN) is a representative of a new class of antidepressants (SNRIs) which inhibit selectively the uptake of serotonin and noradrenaline, but--in contrast to tricyclics--show no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated VEN (given twice daily for 14 days) induced adaptive changes in the alpha 1-adrenergic, dopamine and serotonin systems, similar to those reported by us earlier for tricyclic antidepressants. The results indicate that VEN potentiates the clonidine-induced aggressiveness and the methoxamine-induced exploratory hyperactivity, both these effects being mediated by alpha 1-adrenoceptors. VEN increased the hyperlocomotion induced by D-amphetamine and (+/-)-7-OH-DPAT. Neither the apomorphine and quinpirole hyperlocomotion, nor the apomorphine and D-amphetamine stereotypies were changed. VEN did not affect the behavioural syndrome induced by 8-OH-DPAT (a 5-HT1A effect), and decreased both the head twitch reaction induced by L-5-HTP or (+/-)DOI and the hyperthermia induced by trifluoromethylphenylpiperazine, all those effects being mediated by 5-HT2 receptors. Repeated VEN did not change the hypothermia evoked by oxotremorine (a central cholinergic agonist). The above results indicate that repeated VEN increases--as do tricyclics--the responsiveness of alpha 1-adrenergic and dopaminergic (mainly D3) systems and decreases the responsiveness of the 5-HT2 system. It may be concluded that the lack of affinity for neurotransmitter receptors is of no importance to the development of adaptive changes in the studied systems, observed after repeated treatment.
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PMID:Pharmacological effects of venlafaxine, a new antidepressant, given repeatedly, on the alpha 1-adrenergic, dopamine and serotonin systems. 1022 39

Reflecting its potent inhibition of serotonin (5-HT) reuptake (accompanying paper), S33005 blocked spontaneous tail-flicks induced by parachloroamphetamine in rats. This action was mimicked by the 5-HT reuptake inhibitor, citalopram, and the 5-HT/norepinephrine (NE) reuptake inhibitor, venlafaxine, whereas the preferential NE reuptake inhibitor, reboxetine, was inactive. Consistent with its less potent interaction with NE transporters, higher doses of S33005 attenuated induction of hypothermia by reserpine, an action mimicked by reboxetine and venlafaxine, whereas citalopram was ineffective. In mice, S33005 reduced immobility in forced-swim and tail-suspension procedures. It also inhibited marble-burying behavior and suppressed aggressive behavior between resident and intruder animals. In rats, S33005 generalized to a discriminative stimulus elicited by citalopram and attenuated hypnotic-sedative actions of the alpha2-adrenoceptor agonist, S18616. For these parameters, S33005 was a more potent agent (median, 1.2 mg/kg, s.c.) than venlafaxine, citalopram, reboxetine, or the tricyclic agent, clomipramine. Even at markedly higher doses (40.0-80.0 mg/kg, s.c.), S33005 little affected motor behavior. S33005 (10.0 mg/kg, s.c.) also increased responses in a learned helplessness paradigm in rats, whereas venlafaxine was ineffective. Finally, in a rat chronic mild-stress model, S33005 dose- (2.5-40.0 mg/kg) and time- (2-5 weeks) dependently enhanced sucrose consumption. Venlafaxine was likewise active in this procedure. In conclusion, in line with its inhibition of 5-HT and (less potently) NE reuptake, S33005 is active in a broad range of models suggestive of antidepressant activity. It exerts its actions more potently than venlafaxine and clomipramine, and its overall profile is distinct from those of citalopram and reboxetine.
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PMID:S33005, a novel ligand at both serotonin and norepinephrine transporters: II. Behavioral profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. 1145 19