Drugs online research references
Ann Neurol. 1983 Feb;13(2):160-4.
Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system.
Botney M, Fields HL.
Trycyclic antidepressants are often effective in the management of neuropathic pains. To elucidate the mechanism of tricyclic-induced analgesia, amitriptyline and other drugs were injected into lightly anesthetized rats either systemically or via lumbar intrathecal cannulas. Analgesia was assessed by measuring the latency of the tail flick reflex. Using this model, intrathecal amitriptyline (30 micrograms) significantly enhanced the analgesic effect of an intraperitoneal dose of morphine (0.5 mg/kg) that by itself produced no measurable effect. Given systemically, amitriptyline (30 or 100 micrograms intraperitoneally) was ineffective. Cocaine (30 micrograms) also potentiated morphine analgesia, but iprindole, a tricyclic antidepressant with a very weak inhibitory effect on monoamine uptake, was ineffective. This enhancement of analgesia by intrathecal amitriptyline was prevented by pretreating the rats with p-chlorophenylalanine (300 mg/kg). These results are consistent with the hypothesis that amitriptyline produces analgesia by blocking serotonin uptake and therefore enhancing the action of serotonin at the spinal terminals of an opioid-mediated intrinsic analgesia system.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6219612&dopt=Abstract
Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(2):261-70.
Immediate effects of 14 non MAOI antidepressants in rats with spontaneous petit mal-like seizures.
Warter JM, Tranchant C, Marescaux C, Depaulis A, Lannes B, Vergnes M.
Clinique Neurologique, Hopital Civil, Strasbourg, France.
1. Wistar rats of a strain presenting spontaneous petit mal-like seizures were injected intraperitoneally with graded doses of 14 non-monoamine oxidase inhibitor antidepressants and the immediate effects on behavior and the EEG were recorded. 2. Amineptine and nomifensine, the two drugs interacting with dopaminergic neurotransmission, reduced the duration of spontaneous spike-wave discharges (SWD) and were thus potentially antiepileptic. 3. Trazodone increased SWD duration. 4. The antidepressants, imipramine-like (imipramine, chlorimipramine, desipramine, metapramine and amitriptyline) and non-imipraminic (minaprine, maprotiline, viloxazine, mianserin, fluvoxamine and indalpine), and the 3 noted above, had potentially convulsive effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2106711&dopt=Abstract
Ciba Found Symp. 1979;(74):157-66.
Adrenergic and serotonergic mechanisms in depression and their response to amitriptyline.
Coppen A, Wood K.
Our investigations into the chemical pathology of the affective disorders have indicated that depressed patients not only have significantly reduced rates of accumulation of 5-hydroxytryptamine (5-HT) into their blood platelets but their peripheral alpha-adrenoreceptors are supersensitive. Investigations into the mode of action of amitriptyline have centred on these abnormal adrenergic and serotonergic mechanisms in depressed patients. We have not detected any significant relationship between blood platelet 5-HT re-uptake inhibition and therapeutic response to amitriptyline in depressed patients, although there is a significant correlation with plasma levels of the drug. It is interesting to note that nortriptyline, the major metabolite of amitriptyline, blocks the alpha-adrenoreceptor but the degree of blocking of this supersensitive receptor is significantly correlated to poor outcome. Amitriptyline does not appear to correct these abnormal mechanisms in depressed patients. These results are discussed with reference to other pharmacological actions of amitriptyline and other antidepressant drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=261682&dopt=Abstract
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