Nomifensine, Imipramine and Placebo in Depressed
Outpatients

Rickels, Karl; Cc, Weise; Sandler, Kenneth R.; Schless, Arthur P.; M, Zal; Norstad, N

doi:10.1159/000468602

Cited by 15 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that pure monoamine uptake inhibitors that mimic COC's action on monoamine transporters (i.e. nomifensine, mazindol, bupropion) or have a higher selectivity to the DA transporter (GBR‐12909) are weak reinforcers in animals, not addictive in humans, and typically induce indifferent or aversive subjective effects (Rickels et al ., 1982; Chait et al ., 1993). It is also known that i.v.…”

Section: Discussionmentioning

confidence: 99%

The role of peripheral Na+ channels in triggering the central excitatory effects of intravenous cocaine

Brown

Kiyatkin

2006

Eur J of Neuroscience

View full text Add to dashboard Cite

While alterations in dopamine (DA) uptake appear to be a critical mechanism underlying locomotor and reinforcing effects of cocaine (COC), many centrally mediated physiological and affective effects of this drug are resistant to DA receptor blockade and are expressed more quickly following an intravenous (i.v.) injection than expected based on the dynamics of drug concentration in the brain. Because COC is also a potent local anesthetic, its rapid action on Na+ channels may be responsible for triggering these effects. We monitored temperatures in the nucleus accumbens, temporal muscle and skin together with conventional locomotion during a single i.v. injection of COC (1 mg/kg), procaine (PRO, 5 mg/kg; equipotential anesthetic dose), a short-acting local anesthetic drug that, like COC, interacts with Na+ channels, and cocaine methiodide (COC-MET, 1.31 mg/kg, equimolar dose), a quaternary COC derivative that is unable to cross the blood-brain barrier. In this way, we explored not only the importance of Na+ channels in general, but also the importance of central vs. peripheral Na+ channels specifically. COC induced locomotor activation, temperature increase in the brain and muscle, and a biphasic temperature fluctuation in skin. Though PRO did not induce locomotor activation, it mimicked, to a greater degree, the temperature effects of COC. Therefore, Na+ channels appear to be a key substrate for COC-induced temperature fluctuations in the brain and periphery. Similar to PRO, COC-MET had minimal effects on locomotion, but mimicked COC in its ability to increase brain and muscle temperature, and induce transient skin hypothermia. It appears therefore that COC's interaction with peripherally located Na+ channels triggers its central excitatory effects manifested by brain temperature increase, thereby playing a major role in drug sensing and possibly contributing to COC reinforcement.

show abstract

Section: Discussionmentioning

confidence: 99%

The role of peripheral Na+ channels in triggering the central excitatory effects of intravenous cocaine

Brown

Kiyatkin

2006

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…procaine) are not addictive, suggesting that this action alone cannot explain the abuse potential of cocaine. Similarly, although cocaine is a potent inhibitor of monoamine uptake, other drugs with a similar action have either no or very weak addictive properties (Rickels et al, 1982;Chait et al, 1987) suggesting that monoamine uptake inhibition alone is also insuf®cient to explain the addictive potential of cocaine. It is conceivable therefore that a combination of both monoamine uptake inhibition and a local anaesthetic action is critical for the unique abuse potential of cocaine.…”

Section: Responses To Cocaine After Da Receptor Blockadementioning

confidence: 99%

Dopamine‐independent action of cocaine on striatal and accumbal neurons

Kiyatkin

Rebec

2000

Eur J of Neuroscience

View full text Add to dashboard Cite

Increasing evidence suggests that dopamine (DA) mechanisms alone cannot fully explain the psychoemotional and behavioural effects of cocaine, including its ability to induce drug-taking behaviour. Although it is known that cocaine, after intravenous administration or smoking, may reach brain levels high enough to inhibit Na+ transport, the role of this action remains unclear. To examine the contribution of local anaesthetic and DA mechanisms to changes in striatal and accumbal neuronal activity induced by cocaine, single-unit recording was combined with iontophoresis in awake, unrestrained rats. Most spontaneously active and glutamate-stimulated neurons were highly sensitive to brief cocaine applications (0-40 nA); cocaine-induced inhibitions occurred at small ejection currents (0-5 nA), were dose-dependent, highly stable during repeated applications and strongly dependent on basal activity rates. These neuronal responses remained almost unchanged after systemic administration of either a selective D1 antagonist (SCH-23390, 0.2 mg/kg) or a combination of SCH-23390 (1 mg/kg) and eticlopride (1 mg/kg), a D2 antagonist. Whereas SCH-23390 alone had a weak attenuating effect, no effect and even a slight enhancement of responses to cocaine occurred in fast-firing glutamate (GLU)-stimulated units after the combined blockade of D1 and D2 receptors. Responses to cocaine were mimicked by iontophoretic procaine (0-40 nA), a short-acting local anaesthetic with minimal effect on DA uptake. Procaine-induced inhibitions occurred at the same low currents, had a similar time-course, and were also strongly dependent on basal discharge rate. Our data support the existence of a DA-independent mechanism for the action of cocaine involving a direct interaction with Na+ channels. Although further studies are required to clarify this mechanism and its interaction with other pharmacological and behavioural variables, a direct interaction with Na+ channels may contribute to changes in neuronal activity induced by self-injected cocaine, thereby playing a role in mediating the psychoemotional and behavioural effects of this drug.

show abstract

“…This improvement is almost certainly because the newer antidepressants have negligible affinity for muscarinic, histamine HI and a ,-adrenergic receptors (Richelson and Nelson, 1984). With the possible exception of maprotiline (Crawford et al, 1975), the second generation antidepressants are better tolerated than the tricyclics (eg see Ekdawi, 1975;Rickels et al, 1982;Denckar and Petersen, 1988;Dunbar, 1989) and are much safer when taken in overdose (Cassidy and Henry, 1987;Henry, 1989;Dunbar, 1989). It should be remembered, however, that side-effects resulting from the pharmacological actions of these drugs cannot be avoided, for example nausea, vomiting and gastrointestinal disturbances with the 5-HT reuptake inhibitors, and unpredictable adverse reactions have occurred which forced the withdrawal of zimeldine and nomifensine and handicapped the development of bupropion.…”

Section: Monoamine Reuptake Inhibitorsmentioning

confidence: 99%