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Comparison of tricyclic antidepressants in rabbits: antinociception and potentiation of the noradrenaline pressor responses
i i i!!i;i !!ilii!i!i 3i2
dia os s, Visual average
characte~stics are more important than seemed t o differentiate between ~atients wi~h a
P. T. LascelIes, P. R. Evans, H. t~erskey When pain arises for psychological reasons the subjective experience is qualitatively indistinguishable from pain caused by organic lesions. Similar words are used to describe it. The possibility exists of a physiological difference between patients w i n painful organic lesions and patients with pain but without an organic lesion; Mean levels and diurnal changes of plasma cortisol have been measured intwo such groups of patients, numbering 25 persons, and significant differences found between t i l e groups, those with organic lesions confirmed the hypothesis that physiological differences exist i n t h e psychological origin and pain due to organic disease. A tendency was also present for both groups to have raised mean plasma cortisol va?ues: thus the physMogical differ' once in this case is one of degree. Both groups showed a similar tendency to reduced diurnal variation fin the level of plasma cortisol. The best biochemical method to discriminate pain of organic origin from pain of psychological origin is the measurement of plasma l l-hydroxycorticosteroids at 9 a.m .
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.
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PHARMACOLOGY
Cempad~on of
trieye~ie a n t i d e p r e s s a n t s in rabNts: antinoeieeption and p,~en~iation , f ~he neradrenaijne p r e s s e r v e , p , n s e ,
L Saarnivaara and M J° Mattita, Psyc/wpharmaeotogia (BerL), 35 (1974) 221-236 There are reports that imipramine and some other tricyclic antidepressants diminish pain reaction in laboratory animals and are useful in relieving various types of human pain For these reasons the antinocicepdve effect on rabNt's dental pain of J0 cricyclic antidepressants (2-5 mg/kg, i.v.) was investigated. The effect on morphine analgesia, the potentiation of pressor responses in conscious rabbits a l ~ d ~ e receptor desensitization on the r a b b t s ~solated aortic spiral were also studied. Tertiary amines ~mipramine, amitriptyli~e, a, xep~e and trimipramine were most andnociceptive but in~-?rior to 5 mg/kg o~~"morphmeo " They were a~so most potent ~a enhancing the mot= phine analgesia. The secondary amines desipramine and nortriptyl~ne were tess antinociceptiveo The effect of opipramo~ and imipramine N oxide w~re inconsistent. Dio ~
.
Fine and nor, followed by Opipramol, amitrip~yline and iprindole
~ibe~zepige;
A. D. Sherman and G. F, Gebhart, Life Sci., 15 (1975) 1781-1789 Several independent Iines of evidence indicate that the periaqueductal cer~tra~ gray matter may b e at least one central site where morphine initiates a~ analgesic a!SO being importan~ t o antinociceptive mechaNsms per se. ef glutamate levels in the peria~ quedue~a| ~entral g?ay and ~nt~e :hypethalamus of mice following various treatments. not stressi significantly reduced the ~evel of glutamate in the central g~a~ In the central gray the admiNs tration of morphine O mg/kg, see.)before the exposure to pain significantly ino creased glutamate levels. In the hypothalamus morphine given before pain ca ~sed a further decrease ing|utamate level. The effects of morpNne were prevented by nalexone. Pentobarbital and chlorpromazine were without eft:oct on the glutamate love1 in the central gray suggesting a drug-si:ecific response for this brain area. These data do clearly indicate that glutama~:e may represent a useful neurochemicat indicator of ~he areas in~o!ved in the perception of pain and the antinociceptive action of morphine.
~, Ha L :
depNtien
discrete reggo~ o~: rat brain
J: Neu,~oehem:i 24 (1975) 487-493
The r0ie of ~a!cium in events ~ndertying the actions of opiates has bee~ a subjec~ ofinteres~in recent yearS: Inthis paperthe effects of morphine °in ,,h,o' o~ ::egiona~ Ca ~; leve!s i~ rat brain are repofed. Ti;sue calcium levels were determined by a~:omic abgerp~ien .~:.~Ctrescopy, The administration of a single dose of morphine predicted a decrease of tissue calcium inthe rat brain. This decrease was observed to be linear, dose dependent, time dependen~ and to occur to an equa! degree in g discre:e brai~_ regmns, P e ~ dep~etmn occurred at 3~ ram. Fins effec~ of mo~:phine wa~ .-k ~ : nalexene a ~ d exhiNted e f stereospecificity. Differentiation of t~is response uslng reserpine a~d ~aloxoae ~adicated the possibility of caIcium pools i~ ~he ceg~ra|:nervons Systeml ~ is S~gges~ed that the loss of membra~eobouad calcium may be responsible for the changes in ~he release of neurotransmitters and may play a Nadamenta~ rein in opiate mechamsm of action.
dia os s, Visual average
characte~stics are more important than seemed t o differentiate between ~atients wi~h a
P. T. LascelIes, P. R. Evans, H. t~erskey When pain arises for psychological reasons the subjective experience is qualitatively indistinguishable from pain caused by organic lesions. Similar words are used to describe it. The possibility exists of a physiological difference between patients w i n painful organic lesions and patients with pain but without an organic lesion; Mean levels and diurnal changes of plasma cortisol have been measured intwo such groups of patients, numbering 25 persons, and significant differences found between t i l e groups, those with organic lesions confirmed the hypothesis that physiological differences exist i n t h e psychological origin and pain due to organic disease. A tendency was also present for both groups to have raised mean plasma cortisol va?ues: thus the physMogical differ' once in this case is one of degree. Both groups showed a similar tendency to reduced diurnal variation fin the level of plasma cortisol. The best biochemical method to discriminate pain of organic origin from pain of psychological origin is the measurement of plasma l l-hydroxycorticosteroids at 9 a.m .
.
.
.
PHARMACOLOGY
Cempad~on of
trieye~ie a n t i d e p r e s s a n t s in rabNts: antinoeieeption and p,~en~iation , f ~he neradrenaijne p r e s s e r v e , p , n s e ,
L Saarnivaara and M J° Mattita, Psyc/wpharmaeotogia (BerL), 35 (1974) 221-236 There are reports that imipramine and some other tricyclic antidepressants diminish pain reaction in laboratory animals and are useful in relieving various types of human pain For these reasons the antinocicepdve effect on rabNt's dental pain of J0 cricyclic antidepressants (2-5 mg/kg, i.v.) was investigated. The effect on morphine analgesia, the potentiation of pressor responses in conscious rabbits a l ~ d ~ e receptor desensitization on the r a b b t s ~solated aortic spiral were also studied. Tertiary amines ~mipramine, amitriptyli~e, a, xep~e and trimipramine were most andnociceptive but in~-?rior to 5 mg/kg o~~"morphmeo " They were a~so most potent ~a enhancing the mot= phine analgesia. The secondary amines desipramine and nortriptyl~ne were tess antinociceptiveo The effect of opipramo~ and imipramine N oxide w~re inconsistent. Dio ~
.
Fine and nor, followed by Opipramol, amitrip~yline and iprindole
~ibe~zepige;
A. D. Sherman and G. F, Gebhart, Life Sci., 15 (1975) 1781-1789 Several independent Iines of evidence indicate that the periaqueductal cer~tra~ gray matter may b e at least one central site where morphine initiates a~ analgesic a!SO being importan~ t o antinociceptive mechaNsms per se. ef glutamate levels in the peria~ quedue~a| ~entral g?ay and ~nt~e :hypethalamus of mice following various treatments. not stressi significantly reduced the ~evel of glutamate in the central g~a~ In the central gray the admiNs tration of morphine O mg/kg, see.)before the exposure to pain significantly ino creased glutamate levels. In the hypothalamus morphine given before pain ca ~sed a further decrease ing|utamate level. The effects of morpNne were prevented by nalexone. Pentobarbital and chlorpromazine were without eft:oct on the glutamate love1 in the central gray suggesting a drug-si:ecific response for this brain area. These data do clearly indicate that glutama~:e may represent a useful neurochemicat indicator of ~he areas in~o!ved in the perception of pain and the antinociceptive action of morphine.
~, Ha L :
depNtien
discrete reggo~ o~: rat brain
J: Neu,~oehem:i 24 (1975) 487-493
The r0ie of ~a!cium in events ~ndertying the actions of opiates has bee~ a subjec~ ofinteres~in recent yearS: Inthis paperthe effects of morphine °in ,,h,o' o~ ::egiona~ Ca ~; leve!s i~ rat brain are repofed. Ti;sue calcium levels were determined by a~:omic abgerp~ien .~:.~Ctrescopy, The administration of a single dose of morphine predicted a decrease of tissue calcium inthe rat brain. This decrease was observed to be linear, dose dependent, time dependen~ and to occur to an equa! degree in g discre:e brai~_ regmns, P e ~ dep~etmn occurred at 3~ ram. Fins effec~ of mo~:phine wa~ .-k ~ : nalexene a ~ d exhiNted e f stereospecificity. Differentiation of t~is response uslng reserpine a~d ~aloxoae ~adicated the possibility of caIcium pools i~ ~he ceg~ra|:nervons Systeml ~ is S~gges~ed that the loss of membra~eobouad calcium may be responsible for the changes in ~he release of neurotransmitters and may play a Nadamenta~ rein in opiate mechamsm of action.