Abstract
Agents which interact with alpha- or beta-adrenoceptors were evaluated for efficacy in preventing seizures and death from a lethal dose of cocaine. Rats were first pretreated with the test drug(s), then subjected to an intraperitoneal LD86 of cocaine (70 mg/kg). In this model, control vehicle-pretreated animals developed seizures within six minutes, followed by death within 10 minutes. Significant protection against death was afforded by pretreatment with clonidine (0.25 mg/kg), prazocin (5.0 to 20 mg/kg), propranolol (8.0 to 32 mg/kg), orlabetalol (49 mg/kg). Surviving animals still experienced seizures as judged through behavior and EEG recordings. Phentolamine did not affect the incidence of seizures or death. Two nonadrenoceptor agents were also studied: hydralazine reduced the incidence of death and seizures at 5.0 and 10 mg/kg, but reserpine did not alter the incidence of death or seizures. A combination of prazocin and propranolol did not provide additional protection compared to single agents. We conclude that the pathogenesis of acute cocaine death is complex, and that this toxicity can be antagonized by agents having either central or peripheral effects.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 225-231 |
| Number of pages | 7 |
| Journal | Pharmacology, Biochemistry and Behavior |
| Volume | 36 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1990 |
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Keywords
- Adrenoceptors
- Cocaine
- Death
- Rats
- Seizures
ASJC Scopus subject areas
- Biochemistry
- Behavioral Neuroscience
- Pharmacology
Cite this
Acute cocaine toxicity : Antagonism by agents interacting with adrenoceptors. / Derlet, Robert W.; Albertson, Timothy E.
In: Pharmacology, Biochemistry and Behavior, Vol. 36, No. 2, 1990, p. 225-231.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acute cocaine toxicity
T2 - Antagonism by agents interacting with adrenoceptors
AU - Derlet, Robert W.
AU - Albertson, Timothy E
PY - 1990
Y1 - 1990
N2 - Agents which interact with alpha- or beta-adrenoceptors were evaluated for efficacy in preventing seizures and death from a lethal dose of cocaine. Rats were first pretreated with the test drug(s), then subjected to an intraperitoneal LD86 of cocaine (70 mg/kg). In this model, control vehicle-pretreated animals developed seizures within six minutes, followed by death within 10 minutes. Significant protection against death was afforded by pretreatment with clonidine (0.25 mg/kg), prazocin (5.0 to 20 mg/kg), propranolol (8.0 to 32 mg/kg), orlabetalol (49 mg/kg). Surviving animals still experienced seizures as judged through behavior and EEG recordings. Phentolamine did not affect the incidence of seizures or death. Two nonadrenoceptor agents were also studied: hydralazine reduced the incidence of death and seizures at 5.0 and 10 mg/kg, but reserpine did not alter the incidence of death or seizures. A combination of prazocin and propranolol did not provide additional protection compared to single agents. We conclude that the pathogenesis of acute cocaine death is complex, and that this toxicity can be antagonized by agents having either central or peripheral effects.
AB - Agents which interact with alpha- or beta-adrenoceptors were evaluated for efficacy in preventing seizures and death from a lethal dose of cocaine. Rats were first pretreated with the test drug(s), then subjected to an intraperitoneal LD86 of cocaine (70 mg/kg). In this model, control vehicle-pretreated animals developed seizures within six minutes, followed by death within 10 minutes. Significant protection against death was afforded by pretreatment with clonidine (0.25 mg/kg), prazocin (5.0 to 20 mg/kg), propranolol (8.0 to 32 mg/kg), orlabetalol (49 mg/kg). Surviving animals still experienced seizures as judged through behavior and EEG recordings. Phentolamine did not affect the incidence of seizures or death. Two nonadrenoceptor agents were also studied: hydralazine reduced the incidence of death and seizures at 5.0 and 10 mg/kg, but reserpine did not alter the incidence of death or seizures. A combination of prazocin and propranolol did not provide additional protection compared to single agents. We conclude that the pathogenesis of acute cocaine death is complex, and that this toxicity can be antagonized by agents having either central or peripheral effects.
KW - Adrenoceptors
KW - Cocaine
KW - Death
KW - Rats
KW - Seizures
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UR - http://www.scopus.com/inward/citedby.url?scp=0025351789&partnerID=8YFLogxK
U2 - 10.1016/0091-3057(90)90395-X
DO - 10.1016/0091-3057(90)90395-X
M3 - Article
C2 - 2162541
AN - SCOPUS:0025351789
VL - 36
SP - 225
EP - 231
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 2
ER -