PMID- 8255923
OWN - NLM
STAT- MEDLINE
DCOM- 19940110
LR  - 20190712
IS  - 0091-3057 (Print)
IS  - 0091-3057 (Linking)
VI  - 46
IP  - 1
DP  - 1993 Sep
TI  - Acute cocaine toxicity: the effect of agents in non-seizure-induced death.
PG  - 61-5
AB  - Death from cocaine intoxication results from one or more of the multiple 
      mechanisms including seizures, cardiovascular collapse, or apnea. In the 
      free-moving rat model, continuous seizures are a major cause of death. To study 
      other mechanisms of death unrelated to seizures in this model, we suppressed 
      lethal seizures with diazepam (DZP) and investigated the effect of several 
      pharmacological agents. Rats were pretreated with vehicle alone, diazepam 5 mg/kg 
      alone, or a combination of DZP plus either nifedipine (NIFD) 2 mg/kg, propranolol 
      (PROP) 10 mg/kg, or prazosin (PRAZ) 5 mg/kg. Five minutes after pretreatment, all 
      animals received cocaine 100 mg/kg. Each test group consisted of 15 animals and 
      all agents were given IP. Two animals in each group had cortical electrodes 
      implanted. Animals that received vehicle followed by cocaine had 100% incidence 
      of seizures and death. Those rats that received DZP alone followed by cocaine had 
      no seizures and 53% death. Rats that received DZP plus NIFD or DZP plus PROP had 
      suppression of seizures but no significant change in the incidence of death. The 
      group that received DZP and PRAZ followed by cocaine had no seizures and 13% 
      incidence of death (p < 0.001). Electroencephalogram recordings showed cortical 
      electrical spike activity or spike-and-wave afterdischarges in all animals 
      clinically observed to have seizures. In the absence of clinical seizure 
      activity, no significant cortical spike activity was noted. It is concluded that 
      animals protected from seizures with diazepam can still have nonseizure deaths 
      after high-dose cocaine. The incidence of death in these animals is not reduced 
      with nifedipine or propranolol pretreatment but is reduced with prazosin 
      pretreatment.
FAU - Tseng, C C
AU  - Tseng CC
AD  - Department of Medical Pharmacology and Toxicology, School of Medicine, University 
      of California, Davis 95616.
FAU - Derlet, R W
AU  - Derlet RW
FAU - Albertson, T E
AU  - Albertson TE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Anticonvulsants)
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - I5Y540LHVR (Cocaine)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - Q3JTX2Q7TU (Diazepam)
RN  - XM03YJ541D (Prazosin)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/pharmacology
MH  - Cocaine/antagonists & inhibitors/*poisoning
MH  - Diazepam/pharmacology
MH  - Electrodes, Implanted
MH  - Electroencephalography/drug effects
MH  - Male
MH  - Nifedipine/pharmacology
MH  - Prazosin/pharmacology
MH  - Propranolol/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Respiratory Tract Diseases/chemically induced
MH  - Seizures/chemically induced/physiopathology
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
AID - 0091-3057(93)90317-M [pii]
AID - 10.1016/0091-3057(93)90317-m [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 1993 Sep;46(1):61-5. doi: 10.1016/0091-3057(93)90317-m.